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Biomedical subjects

C S Koh

Publications and source records attributed to C S Koh.

At least 55 records · Page 3Linked to original sources

Low prevalence of immunogenetic markers of IDDM in adult Koreans with diabetes detected on OGTT.

In the Asian populations, it is not uncommon for adult patients with NIDDM to eventually lose beta-cell function and develop IDDM. Accepting that IDDM is an autoimmune disease, which occurs on a genetic background, it could by hypothesized that by measuring autoantibody prevalence and HLA DQ gene polymorphism, known important prediagnostic markers of IDDM, the prevalence of adult-onset IDDM in patients with previously undiagnosed NIDDM patients could be estimated. To do this, anti-GAD prevalence and HLA DQ A1 and DQ B1 polymorphisms after PCR amplification of genomic DNA were analyzed in 121 newly diagnosed diabetic patients of Yonchon cohort and compared to the results with those of 100 matched health control subjects. We also compared the results with those of other populations to assess the difference of genotype distribution. The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 controls had positive antibodies. Among those who were positive, their titer of antibodies to GAD were not high. No statistically significant differences in the distribution of either mean levels of anti-GAD or DQA1 and DQB1 alleles were found comparing NIDDM patients to controls. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the Korean adult control population was similar to that of US Caucasians (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles among recent-onset NIDDM patients, not different compared to controls suggests that diabetes in Korean adults is unlikely to have an autoimmune component to its pathogenesis.

Adult↗

Community-based epidemiologic study on atherosclerotic cardiovascular risk factors.

The present study was undertaken to determine the prevalence of hyperlipidemia and to find out the possible impact of serum lipid profiles on other cardiovascular risk factors in Yonchon County, Korea. Population-based cross-sectional study by random cluster sampling of registered residents over 30 years of age was performed. Out of the 3804 subjects scheduled for the survey, 2520 underwent the actual examination. The prevalence of hypercholesterolemia (serum cholesterol > or = 240 mg/dl) was only 1.2%, whereas that of hypertriglyceridemia (serum triglyceride > or = 250 mg/dl) was as high as 11.3%. The serum levels of cholesterol, triglyceride and HDL cholesterol correlated with anthropometric indices, body mass indices and waist hip ratios. The prevalences of diabetes and/or hypertension increased as either serum cholesterol or triglyceride level increased. In addition, the prevalence rates of obesity, impaired glucose tolerance, hypertriglyceridemia and hypercholesterolemia in its isolated form (free of the others) were much lower than overall prevalence indicating an existence of major overlap among these cardiovascular atherosclerotic risk factors in the form of multiple combinations. Central obesity was found to be an independent associated factor for the aggregation of the conditions related to the increase in cardiovascular risks. The prevalence of hypercholesterolemia in Yonchon County was substantially lower than that previously suggested, albeit that of hypertriglyceridemia was very high. We could also observe a varying degree of transition in cardiovascular risks related to insulin resistance from the rural to the urban area with rapid emergence of non-communicable diseases as a result of modernization.

Adult↗

The level of tumor necrosis factor-alpha producing cells in the spinal cord correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

The levels of tumor necrosis factor (TNF)-alpha producing cells were analyzed in mice with Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Using an ELISPOT assay, we demonstrate an increase in TNF-alpha producing cells in the spinal cords of TMEV-infected SJL/J mice, especially at an active disease stage. The numbers of TNF-alpha producing cells were extremely high in susceptible SJL/J mice compared with the numbers in resistant BALB/c and C57BL/6 mice. TNF-alpha producing cells were also immunohistochemically identified in active lesions of TMEV-IDD at acute as well as chronic stages. The percentage of TNF-alpha producing cells compared with the total number of cells isolated from spinal cords was higher in TMEV-infected SJL/J mice than resistant BALB/c and C57BL/6 mice. Correspondingly, the level of TNF-alpha was much higher in the culture supernatants of both infiltrating cells in the spinal cords and spleen cells from clinically affected animals than that from similarly treated resistant mice. Treatment of virus-infected mice with a mAb specific for TNF-alpha at the beginning of the onset of disease suppressed the development of the demyelinating disease. These findings suggest that TNF-alpha may play an important role in the pathogenicity of TMEV-IDD.

Animals↗

Quantitative lung perfusion scintigraphy in postoperative evaluation of congenital right ventricular outflow tract obstructive lesions.

Improved methods to relieve pulmonary artery stenosis have emphasized the need for an accurate noninvasive method to quantify the pulmonary blood flow. The aim of this study was to compare the roles of Tc-99m MAA perfusion lung imaging, chest x-ray, MRI, and cine-angiography for postoperative evaluation of pulmonary blood flow in patients with congenital right ventricular outflow tract (RVOT) obstructive lesions. Eleven patients underwent chest x-ray, MRI, perfusion lung imaging, and cine-angiography after corrective surgery of RVOT obstruction. The perfusion ratio on lung scans was calculated on the posterior views. The correlation coefficient of the left to right perfusion ratio measured by lung scans obtained with that by visual assessment of chest x-rays, with the most stenotic diameter ratio on MRI and on angiography being 0.57, 0.88 (P < 0.001), and 0.87 (P < 0.001), respectively. Follow-up perfusion lung scans in seven patients, before and after pulmonary artery intervention showed significantly improved perfusion ratios (0.30 +/- 0.11 to 0.70 +/- 0.22; P < 0.001), which were concordant with the clinical findings. The authors conclude that the quantitative perfusion lung scan is the noninvasive method of choice for postoperative evaluation of the pulmonary artery in congenital RVOT obstruction.

Adolescent↗

Epitopes for thyroid-stimulating antibodies in Graves' sera: a possible link of heterogeneity to differences in response to antithyroid drug treatment.

To evaluate the extent and clinical relevance of epitope heterogeneity for stimulating TSH receptor antibodies (TSHRAbs), we measured the activity of IgG preparations from 66 untreated patients with Graves' disease using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR and two TSHR chimeras with residues 9-165 (Mc1 + 2) or 90-165 (Mc2) substituted by equivalent residues of the LH/CG receptor. IgG from 68% of patients lose all of the stimulating TSHRAb activity with the chimeras; IgG from 27% lose most of the activity. Thus, we show that 95% of patients have stimulating TSHRAbs that require epitopes on the N-terminal portion of the extracellular domain of the TSHR and demonstrate the importance of epitopes within residues 90-165 for the first time. Heterogeneous epitope distribution, residual activity with one or both chimeras, i.e. with epitopes other than on the N-terminus of the TSHR, occurred in 21 patients (group A). Forty-five patients with homogeneous epitope distribution (group B) had stimulating TSHRAbs that depended only on epitopes on the N-terminus of the TSHR. Patients in group A were more likely to become euthyroid during antithyroid drug therapy and to do so more quickly than group B patients. The CHO-human TSHR cell system described herein appears to be as effective as the FRTL-5 rat thyroid system in stimulating TSHRAb detection; however, the two systems appear to measure different antibody populations in about 30% of cases. Further, stimulating TSHRAb activities measured in the FRTL-5 system tend to correlate better with goiter size and 99mTc pertechnetate uptake, whereas stimulating activities measured in the CHO-human TSHR/chimera system correlate better with free T4 and T3 levels.

Animals↗

The low prevalence of immunogenetic markers in Korean adult-onset IDDM patients.

OBJECTIVE: IDDM is an autoimmune disease that occurs among genetically susceptible individuals. In Asian populations, it is not uncommon for adult patients with NIDDM to eventually lose beta-cell function and develop IDDM. These individuals may be characterized by autoantibodies to GAD and high-risk HLA-DQ alleles, which are unlikely to be prevalent among patients with true NIDDM or in the general population. The objective of the present study was to evaluate and compare the prevalence of these immunogenetic markers in NIDDM patients and healthy nondiabetic individuals from Korea. RESEARCH DESIGN AND METHODS: The prevalences of anti-GAD antibodies and HLA-DQA1 and DQB1 alleles among 121 patients with newly diagnosed NIDDM identified from a population-based study in Yonchon, Korea, and 100 matched healthy control subjects were evaluated and compared. RESULTS: The overall prevalence of anti-GAD antibodies was 1.7% (2 of 121) in patients with previously undiagnosed NIDDM, whereas 1 of 100 control subjects had a positive test for antibodies. Among those who tested positive, titers of antibodies to GAD were not high. No statistically significant differences in the distributions of either mean levels of anti-GAD antibodies or DQA1 and DQB1 alleles were found comparing NIDDM patients with control subjects. Interestingly, the frequency of DQB1*non-Asp-57 and DQA1*Arg-52 alleles in the Korean adult control population was similar to that in the U.S. white population (DQB1*non-Asp-57: 0.431 vs. 0.475; DQA1*Arg-52: 0.492 vs. 0.463). CONCLUSIONS: The low prevalence of anti-GAD antibodies and HLA-DQA1 and DQB1 susceptibility alleles among recent-onset NIDDM patients, which was similar to observations in control subjects, suggests that diabetes in Korean adults is unlikely to have an autoimmune component to its pathogenesis.

Adult↗

Relationships between angiotensin I converting enzyme gene polymorphism and renal complications in Korean IDDM patients.

OBJECTIVES: The prognosis of IDDM is mainly dependent on complicated diabetic nephropathy which is probably determined by both metabolic abnormalities and genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. The insertion(i)/deletion(D) polymorphism in intron 16 of ACE gene is strongly associated with ACE levels, and subjects homozygote for deletion (genotype DD) have the highest plasma values. Recently, it was reported that I/D polymorphism of ACE gene is associated with diabetic nephropathy in Caucasian IDDM patients. We studied the relationship between the ACE gene polymorphism and diabetic nephropathy in Korean IDDM patients. METHODS: The study population consisted of 59 IDDM patients (duration > 5 yrs) and 107 control subjects. IDDM subjects were divided into 2 groups according to the presence or absence of diabetic nephropathy (with nephropathy: n = 31, without nephropathy: n = 28). After extraction of genomic DNA from peripheral blood leukocytes, PCR was performed using the sense primer (5' -GCC CTG CAG GTG TCT GCA GC-3') and anti-sense primer (3'-TGC CCA TAA CAG TGC TTC ATA -5'), respectively. The PCR products were electrophoresed in 2% agarose gels, and DNA was visualized directly with ethidium bromide staining. RESULTS: Frequencies for II, ID and DD genotypes were similar in IDDM subjects and controls (23: 19:17 vs 49:41:17, p = 0.142) and derived allele frequencies for I and D alleles were similar in both groups (0.551:0.449 vs 0.649:0.351, p = 0.098). The ACE genotype distributions were not different in diabetic subjects with or without nephropathy (12:9:10 vs 11:10:7, p = 0.78) and derived allele frequencies were also similar (0.532:0.468 vs 0.571:0.429, p = 0.81). CONCLUSION: The I and D allele frequency in our controls was different compared to ACE allele frequencies of Caucasian populations, but very similar compared to those of Chinese or Japanese subjects. We found that I/D polymorphism of ACE gene is not implicated in the diabetic nephropathy of Korean IDDM patients and may be explained by ethnic differences.

Adult↗

Bone marrow scintigraphy using technetium-99m-antigranulocyte antibody in hematologic disorders.

UNLABELLED: Bone marrow is the primary site for many hematologic disorders. To date, however, no suitable bone marrow imaging method has been found. The present study investigates the usefulness of bone marrow immunoscintigraphy using 99mTc-labeled antigranulocyte antibody (anti-NCA-95) in 31 patients with hematologic disorders. METHODS: One milligram of antibody labeled with 259-370 MBq 99mTc was injected intravenously, and bone marrow images were taken 4 hr later. We also calculated the uptake ratios of lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B). RESULTS: Of 15 patients with aplastic anemia, 7 showed diffusely decreased antibody uptake (L/B = 2.3 +/- 0.8, I/B = 3.0 +/- 0.8) compared to control patients (n = 21, L/B = 8.2 +/- 2.5, I/B = 10.3 +/- 3.1) Six patients had both decreased and increased uptake areas and two had normal to slightly increased uptake. Of those patients receiving various types of therapy for aplastic anemia, all but one showed increased or irregular uptake. The degree of antibody uptake in the bone marrow correlated with peripheral blood analyses (hemoglobin, white blood cells, platelets). Of six patients with myelodysplastic syndrome, four had irregular uptake and two diffusely decreased uptake. Four patients with myelogenous leukemia showed normal uptake, whereas two with lymphocytic leukemia had decreased uptake. Patients with iron deficiency anemia, pure red cell aplasia or thalassemia minor exhibited normal uptake with bone marrow expansion. CONCLUSION: Immunoscintigraphy with antigranulocyte antibody is a useful method for evaluating the bone marrow status of patients with various hematologic disorders.

Adolescent↗

Intestinal leakage of technetium-99m-MDP in primary intestinal lymphangiectasia.

We present a case in which a patient with primary intestinal lymphangiectasia demonstrated abnormal intestinal accumulation of tracer during 99mTc-methylene diphosphonate (MDP) skeletal scintigraphy. Early intestinal leakage with gradual colonic migration and concentration was confirmed by repeat bone scan with serial acquisitions. The mechanism for the intestinal localization of 99mTc-MDP seen in this patient is not clear. Thus, intestinal lymphangiectasia can be a cause for extra-osseous localization of bone scan agents in the intestine.

Adult↗

[A study on the pathogenesis of hepatomegaly in patients with Crow-Fukase syndrome].

We studied pathogenesis of hepatomegaly in Crow-Fukase syndrome. Hepatocytes were isolated from BALB/c mice and cultured with serum or ascites of three patients with Crow-Fukase syndrome. After 24 hours culture, total number of hepatocytes was counted. The levels of human hepatocyte growth factor (h-HGF) in the serum were also measured. In the hepatocyte culture study, the numbers of hepatocytes after 24 hours cultured in the serum of two patients were significantly larger than those of the control group. When the hepatocytes were cultured with patients' serum after corticosteroid therapy, the survival numbers were markedly reduced. The serum levels of h-HGF in our three patients were 0.62, 0.52, 0.53 ng/ml respectively. They were all slightly higher than normal values (< or = 0.39 ng/ml). Our study indicates that in the serum or ascites of patients with Crow-Fukase syndrome, there may be some humoral factors other than h-HGF, which promote proliferation of hepatocyte or protect hepatocyte.

Aged↗

[A study of soluble form of L-selectin in blood of patients with neuroimmunological disorders].

Members of the selection family mediate the first step of leukocyte-endothelial cell interaction in inflammatory lesion. We have examined the soluble form of L-selectin (sL-selectin) in patients with neuroimmunological disorders (48 multiple sclerosis, 2 Balo's sclerosis, 18 Guillain-Barré syndrome, 7 Miller-Fisher syndrome, 8 chronic inflammatory demyelinating polyneuropathy, and 25 human T-lymphotropic virus type-1 associated myelopathy). The levels of sL-selectin were measured by monoclonal antibody-based enzyme immunoassay on serum samples taken from patients with neuro immunological disorders. The level of sL-selectin were significantly decreased in the blood of patient with inactive stage of multiple sclerosis (MS), Guillain-Barré syndrome (GBS), and human T-lymphotropic virus type-1 associated myelopathy (HAM). The levels of sL-selectin in the sera of patients with active phase of MS tended to be high, but not significantly increased. The levels of sL-selectin, however, in the sort of patients with Balo's concentric sclerosis tended to be decreased. Thus, the findings that the serum concentrations of sL-selectin were decreased in stable phase of MS and acute phase of GBS and HAM suggest that sL-selectin may be differently involved in between patients with MS and patients with GBS or HAM.

Adult↗

Concentration and distribution of tumor associated antigens TAG-72 and CEA in stomach cancer.

We measured the concentration and distribution of tumor associated antigens, TAG-72 and CEA, in stomach cancer by in vitro quantitative autoradiography (IV-QAR). Frozen sections of 33 specimens were incubated with varying concentrations of 125I-labeled CEA-79.1 and B72.3 antibodies specific for carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72), respectively. Computer analysis of specific antibody binding gave maximal binding values which were equal to the concentrations of the antigen or epitope. TAG-72 was detected in 25 specimens, at a concentration ranging from 8.4 to 562.9 pmol/g. CEA was detected in 32 of the 33 specimens and its concentration ranged from 8.8 to 525.3 pmol/g. The distribution of TAG-72 by IV-QAR coincided with that of the tumor cells in 41.4% of the pathologic lesions. The distribution of CEA coincided with the tumor cells in 80.5% of pathologic lesions, nearly twice the TAG-72. The concentration of TAG-72 was significantly higher in mucinous adenocarcinoma and mucin containing adenocarcinomas than other types of adenocarcinomas. There was no significant difference in the concentration of CEA among the pathologic types of stomach cancer. In summary, stomach cancer exhibited wide variations in TAG-72 and CEA expression. CEA expression was more frequent and homogeneous than TAG-72.

Adenocarcinoma↗

Insulin restores fatty acid composition earlier in liver microsomes than erythrocyte membranes in streptozotocin-induced diabetic rats.

Alterations of fatty acid composition have been observed in a number of tissues in both experimental and human diabetes. Suppression of delta 6 desaturase in the liver, a key enzyme of fatty acid desaturation, has been reported to be responsible for these phenomena. We measured the fatty acid composition of the liver and the erythrocytes, and examined delta 6 desaturase activities to compare the effect of short-term insulin therapy on the tissues with and without delta 6 desaturase, ie., the liver and the erythrocytes using streptozotocin (STZ)-induced diabetic rats. Linoleic (P < 0.05), palmitic (P < 0.01) and docosahexaenoic (DHA) acid (P < 0.01) were higher and arachidonic (P < 0.01) and oleic acid (P < 0.01) were lower in the liver microsomes of diabetic rats when compared to those in control rats. These alterations were partly reversed with insulin treatment. In the erythrocyte membrane, linoleic (P < 0.01) and stearic acid (P < 0.05) were higher, and palmitic (P < 0.05), palmitoleic (P < 0.01), and arachidonic acid (P < 0.01) were lower in diabetic rats. In contrast to the case of the liver microsomes, however, these alterations were persistently observed after 48 h of insulin treatment. The activities of delta 6 desaturase in diabetic rats were 68% of those of controls (P < 0.05), and increased to 119% of controls after insulin treatment. These results show that insulin restores the fatty acid composition earlier in the liver microsome than in the erythrocyte membrane in STZ-induced diabetic rats. The erythrocyte membrane would not be suitable for the investigation dealing with rapid changes of fatty acid composition.

Animals↗

Development of bone marrow immunoscintigraphy using a Tc-99m labeled anti-NCA-95 monoclonal antibody.

We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as an immunoscintigraphic agent for assessing the state of the bone marrow. Western blotting of human granulocyte extracts with the antibody could confirm that the binding was with the epitope of NCA-95. Immunocytochemical staining of bone marrow aspirates revealed specific uptake of this antibody by granulopoietic cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using 99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone marrow as compared to other organs.

Antibodies, Monoclonal↗

Poor renal uptake of Tc-99m DMSA and Tc-99m MDP in a patient with Fanconi syndrome and near normal glomerular filtration rate.

The authors present a patient with Fanconi syndrome who demonstrated poor renal uptake of Tc-99m DMSA and high urinary concentration of the tracer. Tc-99m DTPA imaging was normal and the creatinine clearance was only minimally decreased. These findings suggest that Tc-99m DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption. A Tc-99m MDP bone scan showed faint renal uptake, as well as diffuse high skeletal uptake, particularly in the spine, demonstrating that the metabolic bone disease associated with Fanconi syndrome can be one of the causes of poor renal visualization on a bone scan.

Bone and Bones↗

Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer.

The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase.

Bone Neoplasms↗

High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non-goitrous autoimmune thyroiditis.

OBJECTIVE: We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment. DESIGN: Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non-goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients. PATIENTS: Ninety patients with non-goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non-goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow-up was 1-8 years. Six patients from the TRBAb-positive non-goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months. MEASUREMENTS: Serum TBII was measured by a radioreceptor assay, TSBAb by using FRTL-5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay. RESULTS: The prevalences of TBII and TSBAb is non-goitrous AT were 47.8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non-goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment. CONCLUSION: The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non-goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are now affected by thyroxine and antithyroid drug treatment.

Adult↗

Prevalence of diabetes and IGT in Yonchon County, South Korea.

OBJECTIVE: To determine the prevalence of diabetes and impaired glucose tolerance (IGT) in Yonchon County of South Korea and to investigate their associated factors. RESEARCH DESIGN AND METHODS: We performed a population-based cross-sectional study with random cluster sampling of residents > or = 30 years of age. Among the 3,804 residents sampled, a total of 2,520 participants had a standard 75-g oral glucose tolerance test and answered a detailed questionnaire. We also collected standard anthropometric data. RESULTS: If the data for participants in the age range of 30-64 years were adjusted to the standard world population, the prevalence of diabetes was 7.2% and the prevalence of IGT was 8.9%. It was observed that the significant factors associated with diabetes were waist-to-hip circumference ratio, serum triglyceride levels, age, systolic blood pressure, family history of diabetes, and locality. CONCLUSIONS: The prevalence of diabetes in Yonchon County was substantially higher than was previously suggested. The risk of diabetes increased with the increased central obesity and metabolic disturbances associated with insulin resistance.

Adult↗