Search PubMed⌕ Search

Biomedical subjects

N Minami

Publications and source records attributed to N Minami.

At least 91 records · Page 5Linked to original sources
PubMed1995

The role of nitric oxide in the baroreceptor-cardiac reflex in conscious Wistar rats.

The role of nitric oxide (NO) in baroreceptor-cardiac reflex function was examined using a NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), in conscious Wistar rats. Mean arterial pressure (MAP) and heart period (HP) relationships were obtained by intravenous injection of graded doses of phenylephrine and sodium nitroprusside (SNP). The baroreflex function was compared before and after L-NAME (10 mg/kg iv), L-NAME (10 mg/kg iv) followed by exogenous NO supplied as SNP (10-20 micrograms.kg-1.min-1 iv), or SNP alone (20 micrograms.kg-1.min-1 iv). To find the effect of changing basal MAP on baroreflex function, the baroreflex function was also examined before and after phenylephrine (8 micrograms.kg-1.min-1 iv) or L-NAME followed by concomitant infusion of SNP and phenylephrine. L-NAME increased basal MAP as well as HP from 104 +/- 1 to 141 +/- 2 mmHg and from 168 +/- 3 to 237 +/- 7 ms, respectively. L-NAME shifted the sigmoid curve in the direction of higher MAP with a significant increase in the gain (gain: control 2.14 +/- 0.15 ms/mmHg, L-NAME 3.70 +/- 0.26 ms/mmHg, P < 0.001). L-NAME together with SNP infusion did not significantly affect the gain, basal MAP, or HP. Infusion of SNP alone shifted the sigmoid curve in the direction of lower MAP but had no significant effect on the gain. An infusion of phenylephrine or L-NAME with concomitant infusion of SNP and phenylephrine increased basal MAP similarly as L-NAME alone did but had no significant effect on the gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Embryo culture in explanted oviducts in mice and cattle.

Developmental block of early embryos is due to the lack of some components in the culture medium and/or caused by inappropriate environmental conditions for embryonic development. It was shown in our experiments that the development of mouse and bovine embryos under the influence of oviducts in vitro can provide us with a model to analyze the oviductal factors that promote embryonic development. In the first experiment, it was shown that mouse zygotes developed to the blastocyst stage when a coculture system with ampulla was applied, and the duration of embryo coculture significantly affected the further development of embryos. In the second experiment, it was shown that the proportion of blastocysts of cleaved ova obtained after coculture with mouse ampulla was significantly higher than that obtained after coculture with a granulosa cell monolayer or culture without cells.

Animals↗
PubMed1995

Activity of smooth muscle phosphatases 1 and 2A in rabbit basilar artery in vasospasm.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage frequently leads to a long-term cerebral artery narrowing called vasospasm. Recently, the involvement of myosin light chain kinase has been found in experimental vasospasm in our laboratory. We therefore measured the activity of serine/threonine protein phosphatases 1 and 2A in the rabbit basilar artery in vasospasm and in vasocontraction to study their role, particularly in regard to vasospasm compared with vasocontraction. METHODS: Vasospasm was produced in the rabbit basilar artery by a two-hemorrhage method. Vasocontraction was induced by local application of KCl or serotonin to the rabbit basilar artery after a transclival exposure. The control animals were treated with saline instead of fresh blood. Serine/threonine protein phosphatase activity in the basilar artery was assayed with the use of [32P]phosphorylase-a as a substrate; protein phosphatase 1 activity was evaluated as protein phosphatase activity in the presence of 1 nmol/L okadaic acid, whereas protein phosphatase 2A activity was assessed as protein phosphatase activity inhibited by 1 nmol/L okadaic acid. RESULTS: Values of mean activity of protein phosphatase 1 in myofibrillar extract were 3.58 +/- 0.26 nmol/min per milligram in the control group, 3.22 +/- 0.12 nmol/min per milligram in the spastic group on day 2, and 3.01 +/- 0.16 nmol/min per milligram in the spastic group on day 4 (a significant decrease in protein phosphatase 1 activity in the spastic group on days 2 and 4). In contrast, these values did not show any significant changes in the KCl and serotonin groups. Values of mean activity of protein phosphatase 2A in cytosolic extract were 0.90 +/- 0.07 nmol/min per milligram in the control group, 0.75 +/- 0.10 nmol/min per milligram in the spastic group on day 2, and 0.62 +/- 0.17 nmol/min per milligram in the spastic group on day 4 (a significant reduction in protein phosphatase 2A in the spastic group on days 2 and 4). There was no evidence of significant changes of protein phosphatase 2A in cytosolic extract in the KCl and serotonin groups. CONCLUSIONS: Protein phosphatase 1 in myofibrillar extract is reported to catalyze the dephosphorylation of myosin light chain and calponin, whereas protein phosphatase 2A in cytosolic extract catalyzes the dephosphorylation of calponin and caldesmon. In addition, the phosphorylation of calponin and caldesmon results in the loss of their ability to inhibit smooth muscle contraction. Therefore, the significant decrease in activity of protein phosphatases 1 and 2A in vasospasm may result in uninterrupted vascular smooth muscle contraction by the preservation of phosphorylation of not only myosin light chain but also calponin and caldesmon.

Animals↗
PubMed1995

Synthesis of a novel dual inhibitor of thromboxane A2 synthetase and 5-lipoxygenase (E3040) via the direct coupling reaction of hydroquinone with 3-pyridinecarboxaldehyde.

Synthesis of a novel dual inhibitor of thromboxane A2 synthetase and 5-lipoxygenase, 5,7-dimethyl-6-hydroxy-2-methylamino-4-(3- pyridylmethyl)benzothiazole (E3040), was accomplished via a new coupling reaction, in which a key intermediate, (3,6-dihydroxy-2,4-dimethylphenyl)-(3-pyridyl)methanol, was easily synthesized in a high yield from 2,6-dimethyl-1,4-benzohydroquinone and 3-pyridinecarboxaldehyde in 6 N hydrochloric acid. The regio isomers of 3-pyridinecarboxaldehyde also gave the corresponding coupling products in high yields.

Benzothiazoles↗
PubMed1995

The mechanism responsible for hypertension in a patient with Guillain-Barré syndrome.

We report a case of hypertension associated with Guillain-Barré syndrome. In this case, the circadian variation of blood pressure was interrupted. Examination of neurohumoral factors revealed a hyperactive sympathetic nervous system and an increase in plasma renin activity. Clonidine, which acts centrally to inhibit sympathetic outflow, did not suppress serum norepinephrine or epinephrine. These observations suggest that autonomous hyperactivity of the efferent pathway of the sympathetic nervous system may cause the sustained hypertension throughout the day in this case.

Adult↗
PubMed1995

Pressor effect of recombinant human erythropoietin: results of ambulatory blood pressure monitoring and home blood pressure measurements.

We investigated whether treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (erythropoietin) for a short period would increase their blood pressure. Ambulatory blood pressure monitoring and home blood pressure measurements were used to detect minute increase in blood pressure. Thirty-two patients with a hematocrit of 25% or less received erythropoietin at the dose of 4500 IU/week, by the intravenous route for 8 weeks. Erythropoietin increased the hematocrit from 20.9 +/- 2.1 to 26.2 +/- 2.1%. Erythropoietin elevated mean ambulatory blood pressure by 5 mmHg or more in two-thirds of patients (n = 20; pressor group), while it elevated home mean blood pressure by 5 mmHg or more in one-third of patients (n = 11). An increase in clinic mean blood pressure by more than 5 mmHg was observed only in one-fourth of patients (n = 7). Circadian variation of blood pressure (nocturnal fall and diurnal rise) had been attenuated in the patients of the pressor group before erythropoietin treatment and erythropoietin decreased the nocturnal fall of blood pressure further more. Erythropoietin elevated nocturnal blood pressure more than diurnal blood pressure. Therefore, the increase in blood pressure induced by erythropoietin was detected more reliably by ambulatory blood pressure monitoring. There was no relation between the change in hemoglobin concentration and the increase in ambulatory blood pressure induced by erythropoietin. Erythropoietin tended to decrease cardiac output and plasma volume while it increased total peripheral resistance. It also decreased plasma norepinephrine and vasopressin levels but did not affect other humoral factors. Although the pressor effect of erythropoietin treatment for 8 weeks at the dose of 4500 IU/week was not evident on clinic blood pressure measurements, any increase in blood pressure determined by ambulatory blood pressure should be treated carefully to reduce the risk of a cardiovascular complication in patients receiving hemodialysis.

Aldosterone↗
PubMed1995

Decreased plasma tissue factor pathway inhibitor levels in patients with thrombotic thrombocytopenic purpura.

We measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.

Adolescent↗
PubMed1994

Characterization of a novel cofilin isoform that is predominantly expressed in mammalian skeletal muscle.

Cofilin is an actin-modulating protein of 20 kDa, which is widely distributed throughout muscle and non-muscle cells. By means of immunoblotting combined with two-dimensional gel electrophoresis, we found that two cofilin variants, muscle type (M-type) and non-muscle type (NM-type), exist in mammals, while a single isoform exists in chickens. During in vitro myogenesis of mouse C2 cells, expression of the M-type cofilin was upregulated. To better understand the nature of the M-type cofilin, we cloned cDNAs encoding M-type cofilin from the cDNA library of C2 myotubes and determined the entire sequence. The deduced peptide sequence contained a nuclear localization signal and a putative actin-binding sequence as reported in NM-type cofilin. The sequence showed 81% identity in the amino acid residues with the mouse NM-type cofilin sequence and, interestingly, higher homology (96% identity) with that of chicken cofilin. The mRNA encoding M-type cofilin, though it contains two variants that differ in the size of their 3'-non-coding sequences, was detected predominantly in heart, skeletal muscle, C2 myotubes, and testis by Northern blotting, while the mRNA for NM-type cofilin was seen in a variety of non-muscle tissues. The presence of the muscle type isoform of cofilin strongly suggests that cofilin is deeply involved in the regulation of actin function not only in non-muscle cells but also in muscle cells.

3T3 Cells↗
PubMed1994

Cyclic AMP-induced depolarization measured by bis-oxonol fluorescence in bovine adrenal medullary chromaffin cells.

Effects of cyclic AMP on membrane potentials were examined by measuring the changes of bis-oxonol fluorescence in bovine adrenal medullary chromaffin cells. 8-Bromo cyclic AMP (8Br-cAMP) or forskolin caused a gradual and long lasting increase of the fluorescence intensity. The effects of 8br-cAMP was blocked by cyclic AMP-dependent protein kinase inhibitor, adenosine-3', 5'-cyclic monophosphothioate, Rp-diastereomer (Rp-cAMPS) and there was no further increase in the fluorescence by 8br-cAMP in the cells depolarized with 56 mM KC1 or gramicidin D. Ouabain or the removal of extracellular K+ ([K+]0 free) which block Na+, K+-ATPase also increased the fluorescence. The effect of 8br-cAMP on the fluorescence was counteracted by ouabain or [K+]0 free and was blocked in the absence of extracellular Na+ but not by tetrodotoxin or the removal of Ca2+ from the medium. These results may suggest that cyclic AMP causes the membrane depolarization by accumulating Na+ through the inhibition of Na+, K+-ATPase in adrenal chromaffin cells.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Nonspecies-specific effects of mouse oviducts on the development of bovine IVM/IVF embryos by a serum free co-culture.

In Experiment 1, development of bovine embryos derived from in vitro-matured (IVM) and in vitro-fertilized (IVF) oocytes was examined under 4 culture conditions: 1) co-culture with mouse ampullae continuously for 8 d, 2) co-culture with mouse ampullae that were replaced with fresh ampullae at 48-h intervals, 3) co-culture with bovine granulosa cell monolayers, and 4) culture in medium alone. Culture medium consisted of tissue culture medium 199 (TCM-199) supplemented with 1% fetal calf serum (FCS). Inseminated oocytes were transferred to each of the culture treatment 24 h after insemination and were cultured for 8 d. The number of blastocysts per number of cleaved ova obtained after co-culture with mouse ampullae (42.9%) was significantly (P<0.05) higher than that obtained after co-culture with granulosa cell monolayers (28.3%) or culture without cells (4.2%). In Experiment 2, the developmental ability of bovine IVM/IVF embryos co-cultured with mouse ampullae supplemented with or without serum was examined. When serum was excluded from the culture medium, 26.4% (33 125 ) of the total number of embryos cultured were able to develop to the blastocysts stage using this co-culture system. This value was comparable to that obtained in a serum-supplemented co-culture system (30.7%; 39 125 ). In addition, the developmental ability of embryos that reached to the 4-cell stage or beyond at 46 to 48 h after insemination was not significantly different when the embryos were co-cultured with mouse ampullae with (38.5 vs 44.6%) or without (37.0 vs 33.8%) serum.

Journal Article↗
PubMed1994

Accuracy and performance of the Terumo ES-H51, a new portable blood pressure monitor.

A high performance portable automatic sphygmomanometer, the Terumo ES-H51 (104 g, 58 x 22 x 92 mm), was newly developed for clinical use as a substitute for auscultation using a mercury sphygmomanometer. This device usually displays blood pressure (BP) values obtained by the Korotkoff sound method (K-method). However, when the device judges that BP values obtained by the K-method are inaccurate or unreliable, it substitutes automatically BP values obtained by the cuffoscillometric method (O-method). The accuracy and reliability of the device was tested by comparing it to the auscultation with the standard mercury sphygmomanometer. The mean difference between BP values obtained by the standard method and those obtained by the K-method were -0.7 +/- 2.9 mm Hg systole (mean +/- SD) and -0.3 +/- 2.6 mm Hg diastole, whereas the difference between the former and those obtained by the O-method were 0.3 +/- 5.7 mm Hg systole and 0.3 +/- 4.3 mm Hg diastole (n = 170). The agreement between the BP values obtained according to each of the two methods using the device and the standard method was within 5 mm Hg for 72% to 93% of both systolic and diastolic readings. Therefore, BP values measured by the ES-H51 are accurate. The ES-H51 is sufficiently small and light to be carried easily anywhere. The objective and reproducible BP information obtained by the present device would be useful in clinical practice.

Adult↗
PubMed1994

Possible involvement of nitric oxide in acetylcholine-induced increase of intracellular Ca2+ concentration and catecholamine release in bovine adrenal chromaffin cells.

The role of nitric oxide (NO) in neurotransmitter release was studied using bovine adrenal medullary chromaffin cells. L-Arginine and sodium nitroprusside (SNP) slightly increased the intracellular free calcium concentration ([Ca2+]i), and the effects of the agents were dependent on the presence of the extracellular Ca2+ ([Ca2+]o), but were not blocked by verapamil (30 microM) or diltiazem (30 microM). SNP enhanced the acetylcholine (ACh)-induced rise in [Ca2+]i in the presence but not in the absence of [Ca2+]o. The effects of L-arginine but not those of SNP were inhibited by N omega-nitro-L-arginine (L-NNA). L-NNA significantly reduced the ACh-induced rise in [Ca2+]i and catecholamine (CA) release, and the reduction was restored by L-arginine but not by D-arginine. These results suggest a possible involvement of NO in ACh-induced [Ca2+]i rise and CA release in bovine adrenal chromaffin cells.

Acetylcholine↗
PubMed1994

A high-salt diet alters circadian blood pressure rhythm in Dahl rats.

To determine whether salt loading and salt sensitivity are related to the circadian variation in blood pressure (BP), we studied the circadian rhythm of BP in Dahl rats. Thirteen Dahl salt-sensitive (Dahl-S) and 14 salt-resistant (Dahl-R) rats were fed a high- or low-salt diet after weaning. Mean arterial pressure (MAP) and heart rate (HR) were measured every 4 sec throughout 24 hr in freely moving rats, and the data obtained were analyzed quantitatively by the cosinor method. MAP mesor was significantly elevated in Dahl-S rats on a high-salt diet (SH), as compared with those on a low-salt diet (SL), but there was no difference in the MAP mesor between Dahl-R rats on a high-salt diet (RH) and those on a low-salt diet (RL). MAP amplitude was significantly greater and HR amplitude was smaller in SH rats than in SL rats; the amplitudes of MAP and HR in RH rats were similar to those in RL rats. MAP acrophase was significantly delayed in SH and RH rats as compared with SL and RL rats, respectively; the time delay in the MAP acrophase was not accompanied by a synchronized delay in HR acrophase. The time delay in MAP acrophase was greater in SH rats than in RH rats. These results indicate that salt loading influences the amplitude and acrophase of BP, and that the effect of salt loading on circadian BP rhythm is modulated by salt sensitivity.

Animals↗
PubMed1994

Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland.

Developmental changes in the hormonal effects on the concentration of epidermal growth factor (EGF) in the rat submandibular gland were investigated. The level of EGF in the gland gradually increased with age from 4 up to 8 weeks of age; thereafter it increased markedly, reaching a plateau level at 12 weeks of age in both male and female rats. A significant sex difference in EGF levels was observed between 8 and 14 weeks, the level in the males being approximately twice as high as that in the females at 12 and 14 weeks of age. Castration of male rats decreased EGF to about the same level as that of control females. Treatment of castrated rats with testosterone propionate (TP) restored EGF to the levels in control male rats. Ovariectomy and/or administration of oestradiol-17 beta to ovariectomized rats had no apparent effect on EGF concentration. These findings indicate that the sex difference in EGF concentration can be attributed to the level of endogenous androgens. In addition, hypophysectomy of male rats caused a remarkable decrease in submandibular gland EGF to about 7% of the normal level. This reduction was significantly, although not completely, restored by the administration of TP, triiodothyronine (T3) or GH. Moreover, giving TP with T3 or with GH or both together had additive effects on the increase in EGF levels in hypophysectomized rats. These results provide evidence that EGF in the submandibular gland is regulated multihormonally by at least TP, T3 and GH.

Aging↗
PubMed1994

Compliance with long-term dietary salt restriction in hypertensive outpatients.

Eighty hypertensive outpatients were recruited for a dietary salt restriction program to examine long-term compliance. Twenty-four-hour urine samples were collected repeatedly (7.9 +/- 2.6 times, mean +/- s.d.) during a follow-up period of 6.4 +/- 1.7 years. After initial urine collection, nutritional education was carried out by dietitians to reduce dietary salt intake to 8 g/day or less. After every urine collection, the subjects were given advice by doctors on salt restriction, if necessary. The mean 24-hour urinary salt excretion (U-NaCl) and the mean urinary salt/creatinine ratio (U-NaCl/U-Cr) varied considerably both among and within individuals. U-NaCl/U-Cr, but not U-NaCl, in females was significantly higher than that in males, and in middle-aged subjects than in young subjects. U-NaCl and U-NaCl/U-Cr tended to decrease in the summer. In spite of the repeated educational effort, neither U-NaCl nor U-NaCl/U-Cr was different in the first control samples from that in the last samples. When 57 subjects were divided into three groups according to the urinary salt excretion level, U-NaCl was consistently higher during a follow-up period in the high-salt excretion group than in the mid-salt excretion group, while U-NaCl in the low-salt excretion group was initially lower than, but finally similar to, that in the mid-salt excretion group. These results suggest that: (1) multiple 24-hour urine samplings are required to assess urinary salt excretion in individuals; (2) the influence of age and sex should be taken into account in interpreting U-NaCl/U-Cr; and (3) it seems difficult to achieve long-term dietary salt restriction as a non-pharmacologic treatment of hypertension in an outpatient clinic.

Adult↗
PubMed1994

Pharmacological evidence for regulation of Na(+)-Ca++ exchange by Ca++/calmodulin-dependent protein kinase in isolated bovine adrenal medullary cells.

The mechanism of the regulation of Ca++ influx via Na(+)-Ca++ exchange in response to Na+ deprivation was studied in bovine adrenal medullary cells. Protein kinase inhibitors staurosporine and (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl2,3,9,10-te trahydro-8, 11-epoxy-1H,8H, 11H-2,7b, 11a-triazadibenzo[a,g]cycloocta[c,d,e]trinden- 1-one depressed Na+ deprivation-induced 45Ca++ uptake and catecholamine secretion in a concentration-dependent manner. However, 1 mM dibutyryl cyclic AMP and 1 microM forskolin, an activator of adenylate cyclase, had little effect on Na+ deprivation-induced 45Ca++ uptake and catecholamine secretion. Dibutyryl cyclic GMP (1 mM) and muscarine (30 microM), which increased intracellular cyclic GMP level via stimulation of muscarinic receptors, had also little effect on the responses. Although the phorbol esters 12-O-tetradecanoyl-phorbol-13-acetate and phorbol 12,13-dibutyrate, activators of protein kinase C, enhanced Na+ deprivation-induced catecholamine secretion, these compounds failed to affect Na+ deprivation-induced 45Ca++ uptake. On the other hand, a variety of calmodulin antagonists such as calmidazolium, trifluoperazine, pimozide and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited Na+ deprivation-induced 45Ca++ uptake and catecholamine secretion in a concentration-dependent manner. Furthermore, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipera zin e, which is known as an inhibitor of Ca++/calmodulin-dependent protein kinase II, also reduced Na+ deprivation-induced 45Ca++ uptake and catecholamine secretion. Chelation of intracellular Ca++ with Quin-2 acetoxymethyl ester resulted in a decrease in Na+ deprivation-induced 45Ca++ uptake. However, these compounds that inhibited the Na+ deprivation-induced responses in the cells did not cause solely nonspecific and direct inhibition on Na(+)-Ca++ exchanger. These pharmacological observations suggest that Ca++/calmodulin-dependent protein kinase is involved in the regulation of Na(+)-Ca++ exchange in bovine adrenal medullary cells.

Adrenal Medulla↗
PubMed1994

Pressor effect of recombinant human erythropoietin: results of home blood pressure measurements in hemodialysis patients.

We investigated whether the treatment of anemic hemodialysis patients with a low dose of recombinant human erythropoietin (rHEpo) for a short period would increase the blood pressure (BP). Home BP measurements were used to detect minute increases in BP. Fifty-one anemic patients on maintenance hemodialysis with a hematocrit of 25% or less received rHEpo at the dose of 4500 IU/week by the intravenous route for 8 weeks. Overall, rHEpo did not increase the BP whether measured at home or in the clinic (causal BP). Hemoglobin concentration increased significantly from 7.1 +/- 0.7 to 8.8 +/- 0.7 g/dl. Patients were classified into two groups according to the change in mean (M) home BP induced by rHEpo: a pressor group (delta MBP > or = 5 mmHg, n = 17) and a non-pressor group (delta MBP < 5 mmHg, n = 34). The hemoglobin concentration rose significantly in both groups, but there was no change in casual BP. Home blood pressure measurements showed a gradual and continuous rise in BP in the pressor group, but not in the non-pressor group. Patients administered antihypertensive medications before rHEpo treatment accounted for 88% of the former and 50% of the latter groups. Two patients with malignant nephrosclerosis were included in the pressor group. The findings indicate that rHEpo, even given at a low dose for a short period, elevates the BP, as determined by home BP measurement, but not by casual measurements obtained in the clinic.

Adult↗