Biomedical subjects

H Iida

Publications and source records attributed to H Iida.

At least 181 records · Page 10Linked to original sources

PubMed1997

Expression and localization of annexin V and annexin VI during limb bud formation in the rat fetus.

We have investigated the expression and the localization of annexin V and annexin VI during the development of rat fetal limb buds by immunoblot and immunocytochemical analysis. Neither annexin V nor annexin VI was detectable in undifferentiated mesenchymal cells in limb buds of the day-13-day-16 rat fetus. Skeletal muscles, whose progenitor cells migrate from the somites and appeared in the limb buds at day 14, dramatically expressed annexin VI on the cell surface after differentiation from mononucleated myogenic cells into multinucleated myotubes. At day 16 both annexin V and annexin VI were found to be expressed in differentiated chondrocytes as well as in the perichondrium, a precursor of chondrocytes, whereas the compact layer of mesenchymal cells surrounding a chondrification center (precartilage) did not show any immunoreactivity for either of these proteins. The results suggest a close relationship between the expression of these annexins and cell differentiation of chondrocytes and skeletal muscles during limb but development.

Animals↗

PubMed1997

Grapevine berry inner necrosis, a new trichovirus: comparative studies with several known trichoviruses.

Biological, morphological and serological properties of grapevine berry inner necrosis virus (GINV), the casual virus of grapevine berry inner necrosis disease occurring in Japan, were compared with those of several known trichoviruses. Host range and particle length of GINV were quite similar to those of apple chlorotic leaf spot trichovirus (ACLSV). In ultrathin sections of the infected tissues, GINV particles existed in aggregated masses in the cytoplasm of vascular parenchyma and mesophyll cells. No virus specific inclusion bodies, such as pinwheels, viroplasmas or vesicles were observed. Serological relationships were not found between GINV and ACLSV, grapevine virus A or grapevine virus B. The cDNAs of the 3'-terminal region of the GINV genome were synthesized from poly (A)+RNAs extracted from infected tissues by PCR-selected cDNA subtraction and 3'-RACE PCR. The sequence of the 3'-terminal 2469 nucleotides contained three open reading frames (ORF) encoding a protein with the conserved motifs of RNA polymerase (ORF1), a 39 kDa putative movement protein (ORF2) and a 22 kDa protein (ORF3). The 22 kDa protein expressed in Escherichia coli reacted with antiserum against GINV, indicating that it is the coat protein of GINV. Polymerase and coat protein amino acid sequence comparisons and phylogenetic analyses with nine species of the genera Trichovirus and Capillovirus indicated that GINV is a new trichovirus relatively close to ACLSV.

Amino Acid Sequence↗

PubMed1997

In vivo low density lipoprotein oxidation relates to coronary reactivity in young men.

OBJECTIVES: This study was undertaken to examine the relation of in vivo low density lipoprotein (LDL) oxidation and other lipid risk factors to coronary reactivity in normal subjects. BACKGROUND: Experimental studies have shown that oxidized LDL (ox-LDL) particles are injurious to the vascular wall by impairing its normal vasodilator function. METHODS: We used noninvasive positron emission tomographic (PET) imaging with intravenous dipyridamole to measure coronary flow reserve, a marker of coronary endothelial and smooth muscle function, in 30 healthy men (mean [+/-SD] age 34.4 +/- 3.2 years). As a marker of in vivo LDL oxidation, the autoantibody titer against ox-LDL was measured by the enzyme-linked immunosorbent assay method. RESULTS: Plasma levels of autoantibody titer against ox-LDL were inversely associated with coronary flow reserve (r = -0.42, p = 0.023). High LDL cholesterol levels (above median > 3.0 mmol/liter) were associated with a low coronary flow reserve only in subjects expressing simultaneously high levels of ox-LDL titer (above median). Subjects with simultaneously high levels of LDL cholesterol and ox-LDL titer had lower coronary flow reserve values than subjects in other groups (3.89 vs. > 5.0 in other groups, p = 0.066). CONCLUSIONS: These data provide evidence for the role of ox-LDL in affecting the coronary reactivity in vivo and support the concept that oxidative modification of LDL particles provides a mechanism by which high LDL concentrations exhibit injurious effects on the coronary vascular bed.

Adult↗

PubMed1997

Constitutive activation of mitogen-activated protein kinase pathway in acute leukemia cells.

Mitogen-activated protein (MAP) kinase appears to be one of the key regulators of cell proliferation and differentiation. Very little, however, has been revealed as to how MAP kinase is involved in leukemogenesis. We have studied the activation of the MAP kinase pathway in 100 human primary leukemia cells including 73 acute myelogenous leukemias (AMLs). Forty acute leukemia samples (40% of the total), including 37 AML samples (51% of AML), showed activation of MAP kinase as revealed by the mobility shift of the phosphorylated form of the protein and by in vitro kinase assay. This activation was correlated with MAP kinase kinase activity in these cells. In contrast, none of 14 chronic myelogenous leukemia samples showed the activation of MAP kinase. These results suggest that the MAP kinase pathway is constitutively activated in a subset of primary acute leukemias, and thus indicate the possible role of the constitutively activated MAP kinase in leukemogenesis.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1997

The highly conserved DAD1 protein involved in apoptosis is required for N-linked glycosylation.

BACKGROUND: The tsBN7 cell line is one of the temperature-sensitive mutants for cell proliferation which have been isolated from the BHK21 cell line derived from the golden hamster. It has a mutation in the DAD1 gene encoding a 12.5kDa highly conserved protein through evolution, and enters apoptosis at the restrictive temperature due to this mutation. RESULTS: DAD1 was recovered in light membrane fractions after differential centrifugation. It could not be released from the membrane, even by carbonate extraction, without a detergent. Upon digestion with proteinase K, both N and C terminal portions-but not the middle portions of DAD1- were released from the membrane. Thus, DAD1 appears to be an integral membrane protein in which both termini are located in the cytosol. DAD1 was localized in the endoplasmic reticulum. In accordance with a similarity to the yeast protein Ost2p, which is a subunit of the oligosaccharyltransferase, at the restrictive temperature, loss of DAD1 function caused a defect of N-linked glycosylation in tsBN7 cells resulting in apoptosis. However, tunicamycin, which is known to inhibit N-linked glycosylation did not induce apoptosis in either tsBN7 or BHK21 cells. CONCLUSION: tsBN7 cells have a defect in N-linked glycosylation caused by the loss of DAD1.

Animals↗

PubMed1997

The effects of bupivacaine and ropivacaine on baroreflex sensitivity with or without respiratory acidosis and alkalosis in rats.

Systemic toxicity of local anesthetics causes cardiac and central nervous system (CNS) depression that could be enhanced in the presence of respiratory acidosis. We examined a potential suppression of baroreflex function with bupivacaine and ropivacaine during hypercapnic acidosis or hypocapnic alkalosis. Baroreflex sensitivity (BRS) was randomly tested in rats with one of 13 conditions during intravenous administration of saline (control), bupivacaine 1, 2, or 3 mg/kg, or ropivacaine 2, 4, or 6 mg/kg. The effects of bupivacaine (3 mg/kg) or ropivacaine (6 mg/kg) on BRS were also examined during hypercapnic acidosis or hypocapnic alkalosis. The BRS was assessed using a value of delta heart rate/ delta mean arterial pressure after infusion of phenylephrine (3 micrograms/kg). Both bupivacaine and ropivacaine (at the largest dose) significantly suppressed BRS. Acute respiratory acidosis (pHa 7.24 +/- 0.04, Paco2 63 +/- 4 mm Hg) enhanced BRS. The BRS enhanced during acidosis was also suppressed with bupivacaine and ropivacaine, but less so than in the absence of acidosis. The presence of hypocapnic alkalosis (pHa 7.55 +/- 0.03, Paco2 25 +/- 2 mm Hg) did not affect BRS and reversed BRS suppression caused by both drugs. Thus, bupivacaine and ropivacaine affect neuronal control mechanisms for maintaining cardiovascular stability, and acute changes of respiration could significantly modify such suppression.

Acidosis, Respiratory↗

PubMed1997

The effects of topical and intravenous ropivacaine on canine pial microcirculation.

To assess the direct cerebrovascular effects of ropivacaine, we studied pharmacological responses to its topical and intravenous (IV) administration on vasomotor tone of pial vessels in in vivo experiments using a parietal cranial window in 24 dogs anesthetized with pentobarbital. We directly measured the diameters of pial arteries and veins after the administration of five different concentrations of ropivacaine solution (10(-7) to 10(-3) mol/L) randomly given into the window (n = 10). In six dogs, after pretreating the pial vessels with yohimbine (10(-5) mol/L), the inhibitory action of yohimbine was examined after the application of ropivacaine (10(-3) mol/L). The effects of IV ropivacaine (1 and 4 mg/kg) were also evaluated in the remaining eight dogs. Ropivacaine produced significant constriction of the pial arteries in a concentration-dependent manner (10(-7) to 10(-3) mol/L, P < 0.05) and only exerted a constrictive action on small veins (P < 0.05) at 10(-3) mol/L. Yohimbine had no effect on ropivacaine-induced constriction of pial vessels. IV ropivacaine, 4 mg/kg but not 1 mg/kg, caused pial vascular constriction (large arteries P < 0.005, small arteries P < 0.0001, large veins P < 0.01, small veins P < 0.005) associated with decrease in heart rate (P < 0.001). The results indicate that topical application of ropivacaine constricts pial arterial vessels in a concentration-dependent manner. A large dose of IV ropivacaine produced pial vasoconstriction associated with a decrease in heart rate and no decrease in mean arterial blood pressure. These effects do not appear to be mediated via the mechanism that depends on the activation of alpha2-adrenoceptors. We conclude that ropivacaine in high concentrations could, perhaps directly, cause significant constriction of the central nervous system vasculature.

Administration, Topical↗

PubMed1997

Spinal conduction block by intrathecal ketamine in dogs.

In addition to its use for intravenous (I.V.) anesthesia, ketamine can provide pain relief in humans when administered spinally. To elucidate the mechanisms of intrathecal (I.T.) ketamine analgesia, we observed differences in the effects of I.V. and I.T. ketamine on intraspinal evoked potentials (ISEPs) in 28 dogs anesthetized with pentobarbital. Bipolar extradural electrodes were inserted at the cervical and lumbar regions of the spinal cord for recording descending ISEPs represented by the two negative deflections, Waves I and II. I.V. ketamine 2 and 10 mg/ kg did not affect the amplitude and latency of Wave I, whereas the large dose (10 mg/kg) significantly decreased the amplitude but not the latency of Wave II. I.T. ketamine 1 and 5 mg/kg caused significant dose-dependent decreases in both Wave I and II amplitudes and prolongations of both Wave I and II latencies. These I.T. effects on ISEPs are consistent with previous in vitro observations that ketamine blocks axonal conduction. We conclude that axonal conduction block may contribute to the analgesic mechanism of I.T. ketamine.

Anesthesia, Spinal↗

PubMed1997

Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique.

BACKGROUND: Ropivacaine produces a vasoconstriction of cutaneous vessels in contrast to vasodilation produced by bupivacaine. To evaluate direct spinal microvascular actions of these local anesthetics, the authors investigated the concentration-related effects of ropivacaine and bupivacaine on spinal pial vascular diameters using the spinal window technique. METHODS: Anesthetized dogs (n = 14) divided into two groups (ropivacaine, n = 7; bupivacaine, n = 7) were prepared for measurement of spinal pial vessel diameters by intravital microscopy in a spinal window preparation. The authors administered six concentrations of each drug (10(-8)-10(-3) M) under the window and directly measured the spinal pial arteriolar and venular diameters at sequential times. Physiologic data including mean arterial blood pressure (MAP) and heart rate (HR) were determined before and after topical application of each concentration of the drugs. In additional experiments (n = 18), the action of topical ropivacaine and bupivacaine solution on spinal vessels was evaluated in the presence of yohimbine, prazosin, and propranolol. RESULTS: Ropivacaine significantly constricted whereas bupivacaine dilated pial arterioles and venules, both in a concentration-dependent manner. Microvascular alteration was not blocked with any of the adrenoceptor antagonists tested (yohimbine, prazosin, propranolol), each of which per se did not affect pial vessel diameters. Topical application of ropivacaine or bupivacaine did not induce any change in MAP or HR. CONCLUSIONS: The present results indicate that ropivacaine constricts and bupivacaine dilates the pial vessels of the spinal cord in a concentration-dependent fashion, and the mechanisms involved in such actions do not seem to be mediated via alpha- or beta-adrenoceptor of spinal vasculature.

Amides↗

PubMed1997

Small GTP-binding protein, Rab6, is associated with secretory granules in atrial myocytes.

Rab proteins, a subfamily of small GTP-binding proteins, have been shown to play key roles in regulation of vesicular traffic in eukaryotic cells. In this study, we have intended to identify, the atrial granule-associated Rab proteins that seem to be required for formation or intracellular transport of the granules. Atrial granules contained at least four small GTP-binding proteins, and we have demonstrated by biochemical analysis that one of the small GTP-binding proteins associated with the atrial granules is a Rab6 protein (Rab6p). Rab6p was also detected in highly purified zymogen granules of pancreatic exocrine gland. Immunogold electron microscopy performed on ultrathin cryosections of rat auricle revealed that Rab6p was associated with the atrial granule membranes. Association of Rab6p with the atrial granule membranes was also confirmed by immunodiffusion electron microscopy in agarose-embedded atrial granules. These data indicate that Rab6p is associated with the atrial granules and that it might function in the intracellular traffic of the secretory granules in the atrial myocytes.

Animals↗

PubMed1997

Expression of platelet-derived growth factor in lupus nephritis in MRL/MpJ-1pr/1pr mice.

Platelet-derived growth factor (PDGF) plays an important role in the pathogenesis of mesangial proliferative glomerulonephritis. We examined PDGF expression and glomerular changes in lupus nephritis-prone MRL/MpJ-1pr/1pr (MRL/1) mice. The total number of nuclei per glomerular section and blood urea nitrogen (BUN) level were significantly increased in MRL/1 mice aged 20 weeks compared to those aged 8 weeks. A positive correlation existed between numbers of PDGF beta-chain-positive cells and glomerular cells in MRL/1 mice (r = 0.77, p < 0.01). The BUN level did not differ among MRL/MP-+2 (MRL/n) mice of different ages, but the glomerular cell number increased modestly with age. At the age of 20 weeks, the incidence of crescent formation per kidney tissue ranged from 9 to 32% (mean 19%) in MRL/1 mice but was 0 in MRL/n mice. PDGF beta-chain protein was expressed in the mesangium and crescents in 20-week-old MRL/1 mice but was expressed rarely in the glomeruli of MRL/n mice. These results suggest that the PDGF beta-chain plays an important role in glomerular cell proliferation and crescent formation in murine lupus nephritis.

Animals↗

PubMed1997

Newborn cerebrovascular responses after first trimester moderate maternal ethanol exposure in sheep.

Fetal alcohol syndrome is one of the leading causes of mental retardation in the United States, but the pathogenesis of the associated brain damage is unknown. We tested the hypothesis that neonatal cerebrovascular responses to CO2 and/or hypoxia may be altered by moderate chronic maternal ethanol exposure early in gestation. We studied 26 newborn lambs (1-4 d old). Their mothers had received daily i.v. infusions of either ethanol (1 g/kg; ethanol concentration = 167 +/- 3 mg/dL; mean +/- SEM) or a similar volume of saline for 3 wk during the first trimester. In nine lambs, we studied cerebral responses to CO2 (saline, n = 4; ethanol, n = 5) and in 17 lambs, cerebral responses to hypoxia (saline, n = 7; ethanol, n = 10). Cerebrovascular responses to CO2 were not different between the groups. However, the cerebral vasodilatory response to hypoxemia was significantly attenuated in the ethanol lambs, such that cerebral O2 delivery was not maintained. During severe hypoxia (arterial PO2 = 30 mm Hg), cerebral blood flow increased 106 +/- 23% (mean +/- SEM) above baseline in the saline-treated group, but increased only 32 +/- 15% above baseline in the ethanol-treated group (p < 0.02). Similarly, cerebrovascular resistance in the saline group decreased 52 +/- 6% from baseline, but decreased only 16 +/- 11% in the ethanol group (p < 0.02). We conclude that moderate maternal ethanol infusion early in pregnancy attenuates neonatal hypoxic, but not CO2, cerebrovascular responsivity.

Alcoholism↗

PubMed1997

High frequency of leukemic lymphomas with osteosarcomas but no myeloid leukemias in C3H mice after 239Pu citrate injection.

Female C3H strain mice, which do not spontaneously exhibit frequent bone tumors and myeloid leukemias, were injected intraperitoneally with various doses of 10 to 12,000 Bq/animal of monomeric 239Pu citrate to clarify lifetime carcinogenesis caused by alpha-particles distributed mainly in the skeleton. Survival time was reduced significantly at mean skeletal doses of more than 2.93 Gy and was accompanied by marked life-shortening as compared to the controls due to an earlier increase in neoplastic or non-neoplastic death. Bone tumors, almost all of which were osteosarcomas, were not found in the controls, whereas their incidence increased sharply to a maximum of 96% at 6.92 Gy, then dropped at higher doses (20% at 42.4 Gy). Although lymphoid tumors were present in 20% of the control animals, their incidence dropped to zero at 6.92 Gy, then increased at higher doses (36% at 25.5 Gy). Non-thymic, mostly pre-B cell type, leukemic lymphomas mainly occurred at early time after 239Pu-injection; whereas, in the controls thymic, lymphocytic or histiocytic lymphomas occurred only at a later time. Of the other soft tissue tumors, neither myeloid leukemias nor myelogenous neoplasms were found in the controls or the 239Pu-injected animals. Tumors affecting the lungs, liver, ovaries, and skin were much fewer or not found at mean doses of more than 2.93 Gy. These results indicate dose-dependent, differential tumor induction resulting from bone and lymphoid tumor competition after an injection of plutonium.

Animals↗

PubMed1997

Synovial fluids from patients with osteoarthritis and rheumatoid arthritis contain high levels of parathyroid hormone-related peptide.

High levels of immunoreactive and biologically active parathyroid hormone-related peptide (PTHrP) were detected in synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The levels of PTHrP immunoreactivity in synovial fluids, measured by a two-site immunoradiometric assay (IRMA) which detects hPTHrP(1-72) or longer peptides and a radioimmunoassay (RIA) specific to the carboxy-terminal portion of hPTHrP, were 3.2 +/- 0.3 pmol of hPTHrP(1-86)/l and 61 +/- 7.0 pmol of hPTHrP(109-141)/l in OA patients (mean +/- SE, n = 23), and 4.8 +/- 0.8 pmol of hPTHrP(1-86)/l and 164 +/- 30 pmol of hPTHrP(109-141)/l in RA patients (n = 26). Synovial fluid PTHrP levels distributed above the normal plasma reference ranges in each assay (0.7-2.6 pmol of hPTHrP(1-86)/l; 16-60.6 pmol of hPTHrP(109-141)/l). After concentration using sequential cation-exchange and reverse-phase chromatography, synovial fluid exhibited the activity that stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblastic ROS 17/2.8 cells expressing PTH/PTHrP receptors. The cAMP accumulation activity in synovial fluid was sensitive to coincubation with excess hPTHrP(3-40), a PTH/PTHrP receptor antagonist, and was completely neutralized by preincubation with a monoclonal antibody specific to hPTHrP but not PTH. Immunohistochemical analysis of RA synovium revealed that PTHrP was localized in fibroblast-like cells in the synovial pannus invading articular cartilage. Our data show that PTHrP is produced locally by the diseased synovial tissue and released into synovial fluid at high concentrations, allowing us to hypothesize that PTHrP plays a novel role as a paracrine/autocrine factor in the pathology of OA and RA.

Aged↗

PubMed1997

A remote conference system for image diagnosis on the World-Wide Web.

OBJECTIVE: The World-Wide Web on the Internet enables an exchange of multimedia information among remote desktop computers. Therefore, a teleradiology system using the Web would allow remote consultation with expert radiologists. Our objective was to establish a Web-based prototype system for image interpretation. CONCLUSION: Our system allows a physician to transmit clinically useful images to an expert radiologist at a different location, who can see them on a Web browser and discuss diagnoses with the physician.

Computer Communication Networks↗

PubMed1997

Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15O]CO, and positron emission tomography.

Exaggerated vasoconstriction and blunted vasodilation of peripheral resistance arteries to various vasoactive agents characterize patients with IDDM. We characterized the hemodynamic effects of insulin in skeletal muscle in patients with IDDM. Muscle blood flow and blood volume were measured basally and during a high-dose insulin infusion (5 mU x kg(-1) x min[-1]) in seven normotensive patients with IDDM (age, 30 +/- 6 years; BMI, 24.5 +/- 2.0 kg/m2; blood pressure, 124 +/- 12/78 +/- 11 mmHg) and nine matched normal subjects, using [15O]H2O, [15O]CO, and positron emission tomography (PET). Whole-body insulin sensitivity was determined using the euglycemic insulin clamp technique. Insulin-stimulated whole-body glucose uptake was significantly lower in the patients with IDDM (45 +/- 15 micromol x kg(-1) x min[-1]) than in the normal subjects (62 +/- 14 micromol x kg(-1) x min[-1]) (P < 0.05). Insulin increased muscle blood flow by 111 +/- 69% above basal from 3.0 +/- 2.0 to 5.8 +/- 3.0 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in the normal subjects, but only by 42 +/- 30% from 2.0 +/- 0.9 to 2.9 +/- 1.4 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in patients with IDDM (P < 0.05 for change in flow in IDDM vs. normal subjects). The calculated muscle vascular resistances were comparable basally, but higher during hyperinsulinemia in the patients with IDDM (37 +/- 17 mmHg x 100 g x min x ml[-1]) than in the normal subjects (16 +/- 7 mmHg x 100 g x min x ml[-l]) (P < 0.05). Muscle blood volume increased significantly by insulin in both groups without any difference between the groups. We conclude that the ability of supraphysiological concentrations of insulin to stimulate muscle blood flow is blunted in patients with IDDM, because of the inability of insulin to stimulate linear flow velocity rather than blood volume in skeletal muscle. This defect adds yet another defect to the list of abnormalities in vascular function in IDDM, which might predispose these patients to develop hypertension.

Adult↗

PubMed1997

A long-term clinical study on drawn poly-L-lactide implants in orthopaedic surgery.

We have developed an ultra-high-strength drawn poly (L-lactide) (PLLA) with a bending strength of 240 MPa. Seventy-four patients (80 cases) who were treated with this PLLA implant were enrolled in this study. Their ages ranged from 14 to 78 years, and the follow-up period ranged from 4 to 9 years (mean: 5.3 years). Bony union was obtained in all cases. Osteolytic changes were observed in 12 cases (15%) but no late aseptic swelling was noted. Both MRI and roentgenographic findings indicated that the spaces where the PLLA implants were located had not been replaced with bony tissue.

Adolescent↗

PubMed1997

Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and PET.

UNLABELLED: The aim of the present study was to evaluate quantitation of muscle blood flow using [15O]H2O and PET. METHODS: The autoradiographic (ARG) and the steady-state methods using PET were used to measure femoral muscle blood flow. A simulation study was performed to examine the errors due to contamination of radioactivity in the blood content in muscle tissue, statistical noise and delay and the dispersion of the input curve in the ARG method. Five separate paired muscle blood flow examinations were carried out for comparison of the ARG and the steady-state techniques, including measurement of muscle blood volume in each subject. To obtain the normal range for resting muscle blood flow, additional measurements with the ARG method were performed in 16 normal subjects. RESULTS: When the integration time in ARG was increased to 200-300 sec, the errors due to arterial blood volume, statistical noise, delay and dispersion of the input curve were significantly reduced. Muscle blood flow values in the ARG (200 sec) and the steady-state studies were in good agreement, and each provided an estimated accuracy of 5%. Resting muscle blood flow averaged 3.12 +/- 1.55 ml/min.100 g muscle (range 1.43-6.72 ml/min.100 g muscle, n = 18). CONCLUSION: The ARG and the steady-state methods provided consistent blood flow values for skeletal muscle when a long tissue integration time (> or = 200 sec) was applied in the ARG study. Based on the lower effective radiation dose and the shorter total scan duration, the ARG method is favored over the steady-state method in the measurement of muscle blood flow.

Adult↗