Biomedical subjects

Yasuhiro Tanaka

Publications and source records attributed to Yasuhiro Tanaka.

At least 19 recordsLinked to original sources

PubMed2006

Involvement of insect-derived growth factor (IDGF) in the cell growth of an embryonic cell line of flesh fly.

Insect-derived growth factor (IDGF) is the first adenosine deaminase-related growth factor (ADGF) purified from the conditioned medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly). Here we show the requirement of IDGF for the growth of NIH-Sape-4 cells. Growth factor activity was abolished by adsorption of IDGF from the conditioned medium of NIH-Sape-4 cells. In addition, knockdown of IDGF gene expression by RNA interference (RNAi) significantly reduced IDGF secretion from the cells following cell growth inhibition. The IDGF gene was strongly expressed in the hemocytes, and IDGF increased the viability of the larval hemocytes. These data provide evidence that IDGF is required for the growth of NIH-Sape-4 cells and possibly for hemocyte viability.

Animals↗

PubMed2006

Measurement of hepatitis B virus core-related antigen as predicting factor for relapse after cessation of lamivudine therapy for chronic hepatitis B virus infection.

BACKGROUND: Prolonged lamivudine therapy has two major problems: breakthrough hepatitis during treatment and relapse of aminotransferase (ALT) after cessation of the therapy. The aim of this study was to examine factors that could predict ALT flare after stopping lamivudine therapy. METHODS: We analyzed 22 Japanese patients with chronic hepatitis B infection, in whom lamivudine therapy was stopped after HBV DNA level had been gone undetectable (<3.7LGE/ml) during at least six consecutive months. The post-treatment followed up was carried for 28 months in median (range 9-41). HBV core-related antigen (HBcrAg) assay was assessed using newly developed assay. RESULTS: After cessation of lamivudine therapy, 11 patients (50%) had relapsed (reactivation of serum ALT >80IU/l, relapsers) and remaining 11 (50%) did not relapse (non-relapsers). In the univariate comparison of relapsers versus non-relapsers, HBcrAg level at lamivudine cessation point (4.5+/-1.0 versus 3.4+/-0.9; p=0.0145) has been shown as a significant predictive factor for non-relapse. All patients with HBcrAg <3.0logU/ml at the cessation point had no ALT flares. Multivariate analysis on effects of 10 factors (age, sex, cirrhosis, pretreatment ALT level, HBV DNA level, HBcrAg level, mean months till undetectable HBV DNA, duration of undetectable HBV DNA and HBcrAg level at lamivudine cessation point), indicated that HBcrAg level at lamivudine cessation point <3.4log U/ml was the only independent predictive factor for absence of the post-treatment relapse. CONCLUSIONS: HBcrAg level at lamivudine cessation point might be useful as a prognostic predictor of response to lamivudine therapy cessation. The measurement of HBcrAg is a useful additional test for monitoring chronic HBV infection.

Journal Article↗

PubMed2006

Joint properties of cast Fe-Pt magnetic alloy laser welded to gold alloys.

This study investigated the joint properties of a cast Fe-Pt magnetic alloy (Fe-36 at % Pt) laser welded to three gold alloys. The gold alloys used were ADA Type II and Type IV gold alloys, and an Ag-based (Ag-Au) gold alloy. Cast plates (0.5 x 3.0 x 10 mm) were prepared for each alloy. After the cast Fe-Pt plates were heat treated, they were butted against each of the three alloys and then laser welded with Nd:YAG laser at 200 V. Homogeneously welded specimens were also prepared for each alloy. Tensile testing was conducted at a crosshead speed of 1 mm/min. Failure load (N) and elongation (%) were recorded. After tensile testing, the fractured surfaces were examined with the use of SEM. The failure-load values of the group of alloys welded homogeneously were ranked in the order of: Ag-Au alloy > Type IV alloy > Type II alloy > Fe-Pt alloy. The Type IV alloy welded to Fe-Pt alloy had the highest failure-load value among the three alloys tested. The elongation results tended to follow a similar pattern. The results of this study indicated that Type IV gold alloy is a suitable alloy for metal frameworks to which cast Fe-Pt magnetic alloy is laser welded.

Alloys↗

PubMed2006

In vitro reconstruction of a three-dimensional middle ear mucosal organ and its in vivo transplantation.

CONCLUSIONS: These experimental findings suggest the feasibility of artificial middle ear mucosa grafting as an effective treatment for achieving mucosal regeneration after middle ear surgery. OBJECTIVES: Postoperative mucosal regeneration of tympanic cavity and mastoid cavity is of great importance after middle ear surgery. We reconstructed in vitro a three-dimensional middle ear mucosal organ, and assessed its feasibility for regenerative medicine of middle ear-related diseases. MATERIALS AND METHODS: Epithelial cells and fibroblasts were isolated from the middle ear mucosa of rats and propagated by subculturing. An artificial middle ear mucosal organ was reconstructed by overlaying the middle ear epithelial cells on three-dimensional lattices of a collagen gel that had been repopulated with the fibroblasts. In addition, the artificial organ was implanted in the middle ear cavity of rats. RESULTS: The artificial middle ear mucosa consisted of the single layer of epithelial cells, the basal membrane, and the underlying connective tissue. Electron microscopy revealed the presence of tight junctions and adherence junctions on the apical side, and adhesion complexes made of desmosomes. The reconstituted mucosa expressed genes of mucin, strongly suggesting that the artificial middle ear mucosa was capable of secreting mucus proteins. The DiI-labeled artificial middle ear mucosa implanted into the middle ear cavity was well engrafted and associated with host tissues.

Animals↗

PubMed2006

Usefulness and cost effectiveness of cardiovascular screening of young adolescents.

OBJECTIVES: This study was conducted to assess the usefulness of a screening system for cardiovascular disease in Kagoshima, Japan, and to compare its cost-effectiveness with that of a similar system reported in the United States. BACKGROUND: Preparticipation screening of young athletes has been implemented in many countries to prevent sudden death, but sudden death in young nonathletes remains a problem. In Japan, both athletes and nonathletes have been screened for the presence or absence of cardiovascular diseases for more than 20 yr. METHODS: From 1989 to 1997, all seventh graders in schools in Kagoshima, Japan, were screened for cardiovascular disease using a questionnaire and electrocardiogram before physical examination. They were screened again in the same way 3 yr later. One subject newly diagnosed with cardiovascular disease and recommended to limit athletic participation was defined as "high-risk." Situations leading to cases of sudden death were verified with a report from the school in question. RESULTS: Of the initial study population, 99% participated in the program every year. A total of 37,807 subjects, including nine high-risk subjects, were evaluated consecutively for 6 yr. Of these nine subjects, six, including three patients with hypertrophic cardiomyopathy, were nonathletes. Three sudden deaths occurred during the study period; one student was from the high-risk group. The cost of this screening system was lower than that reported in the United States. CONCLUSIONS: Population-based screening for heart disease in this age range is limited by various factors. To analyze the mechanisms of sudden death in adolescents, we, therefore, are in need of a nationwide registry that includes autopsies for all deadly events.

Adolescent↗

PubMed2006

Chronic eosinophilic leukemia with the FIP1L1-PDGFRalpha fusion gene in a patient with a history of combination chemotherapy.

Hypereosinophilic syndrome (HES) was diagnosed in December 2000 in a 43-year-old man on the basis of persistent eosinophilia (11.7 x 10(9)/L) and a normal karyotype of the bone marrow cells. He had developed intra-abdominal non-Hodgkin's lymphoma and in 1992 had received 3 courses of combination chemotherapy with doxorubicin (Adriamycin), cyclophosphamide, vincristine, methotrexate, bleomycin, and prednisolone. The patient was orally given prednisolone (10 mg/day) and cyclophosphamide (50 mg/day) as HES treatment without a subsequent improvement of the eosinophilia. In May 2003, anemia (hemoglobin, 7.9 g/dL) and thrombocytopenia (65 x 10(9)/L) manifested with progressive eosinophilia (21.0 x 10(9)/L) and a small number of blasts. The patient became febrile and was admitted in July 2003. Cytogenetic reexamination of the bone marrow cells disclosed the deletion of 4q12, indicating the presence of a fusion of the Fip1-like 1 (FIP1L1) gene to the plateletderived growth factor receptor alpha (PDGFRalpha) gene and consequently the clonal nature of his hematopoietic cells. DNA sequence analysis demonstrated that the breakpoints of the FIP1L1 and PDGFRalpha genes were present in exon 9 and exon 12, respectively. Treatment with imatinib mesylate (300 mg/day) promptly brought about complete remission. Although a number of similar eosinophilic cases have been reported, our patient may be the first such patient with a history of chemotherapy.

Adult↗

PubMed2006

Multiple granulocytic sarcomas in essential thrombocythemia.

A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and a few blasts were noted in the peripheral blood studied in March 2002. A biopsied specimen of the bone marrow showed myelofibrosis but not a leukemia in August 2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was treated with low-dose prednisolone. In January 2005, she experienced left hip joint pain, and magnetic resonance scanning showed a tumoral lesion in the femoral head. Histological diagnosis of the biopsied mass revealed that it was a granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone scintigraphy showed multiple lesions. She became febrile and red blood cell transfusion-dependent with hepatosplenomegaly and a small number of circulating blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and hepatosplenomegaly; however, she developed a pathologic fracture of the right humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She subsequently died of infection. Granulocytic sarcoma is very rare in essential thrombocythemia, and this patient may be the first reported case of essential thrombocythemia that developed multiple lesions and a pathologic fracture without transformation to overt leukemia.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Prostaglandin E receptor EP1 controls impulsive behavior under stress.

Animals under stress take adaptive actions that may lead to various types of behavioral disinhibition. Such behavioral disinhibition, when expressed excessively and impulsively, can result in harm in individuals and cause a problem in our society. We now show that, under social or environmental stress, mice deficient in prostaglandin E receptor subtype EP1 (Ptger1(-/-)) manifest behavioral disinhibition, including impulsive aggression with defective social interaction, impaired cliff avoidance, and an exaggerated acoustic startle response. This phenotype was reproduced in wild-type mice by administration of an EP1-selective antagonist, whereas administration of an EP1-selective agonist suppressed electric-shock-induced impulsive aggression. Dopamine turnover in the frontal cortex and striatum was increased in Ptger1(-/-) mice, and administration of dopaminergic antagonists corrected their behavioral phenotype. These results suggest that prostaglandin E(2) acts through EP1 to control impulsive behavior under stress, a finding potentially exploitable for development of drugs that attenuate impulsive behavior in humans.

Animals↗

PubMed2005

Glucose oxidase assisted homogeneous electrochemical receptor binding assay for drug screening.

Although the idea of homogeneous electrochemical immunoassay using antibody and an electroactive modified antigen as a probe looks to be very useful for high-throughput drug screening, there have been few reports. One reason for this is the difficulty experienced making an electroactive probe, because the introduction of electroactive compounds to antigens often interferes with the antigen-antibody interaction. To apply a homogeneous electrochemical assay to drug screening, we have designed new probes referring to the information of immobilization on beads which could identify the drug receptor. FK506 (also called Tacrolimus), immunosuppressive agent is modified with ferrocene derivatives as an electron mediator between glucose oxidase and an electrode, at a non-obstructing part. One of the probes still indicated the electrochemical activity as a mediator and had the specific binding capability for FKBP12 (FK506 binding protein). The current decrease in response to the additional FKBP12, detected with constant voltage amperometry using the probe, was observed within 5 min. Then, free FK506 as a leader drug, rapamycin and cyclosporine A as unknown drugs were used as a model for drug screening. Since the order of response currents at the same concentration of each drug reflected their binding constants, it was shown that binding capacity of an unknown drug candidate could be estimated by comparison of response currents between the leader drug and the unknown drug candidate. Thus, this glucose oxidase assisted homogeneous electrochemical drug-receptor binding assay has been proved to be a useful tool for drug screening.

Biosensing Techniques↗

PubMed2005

Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use.

PURPOSE: To evaluate a protocol that allowed the successful generation of DC and OVCA cells, fusion of these two cell types and assessment of stimulatory ability of the fusion cells for clinical use. PATIENTS AND METHODS: Ovarian cancer (OVCA) cells and dendritic cells (DC) were isolated or generated from 22 patients with OVCA and subsequently fused with PEG. The stimulatory ability of fusion cells including T cell proliferation and induction of cytotocic T lymphocytes (CTL) was assessed. In addition, the impact of radiation, freezing and thawing of the fusion cells was evaluated. RESULTS: OVCA cells derived from 22 patients were successfully fused with autologous DC. The created heterokaryons expressed tumor-associated antigens, such as MUC1 and CA-125, and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, CD4 and CD8 T cells derived from patients with ovarian cancer were stimulated by fusion cells and produced IFN-gamma as demonstrated with intracellular staining. Significantly, T cells primed by fusion cells produced MHC class I-dependent lysis of autologous ovarian tumor cells. One cycle of fusion-cell stimulation can maintain the CTL activity up to 25 days. CONCLUSIONS: The fusion of human OVCA cells and DC created immunogenic cells capable of stimulating CD4 and CD8 T cells. The effects of the processes required for preparing a vaccine for clinical use, including freezing and thawing and irradiation, do not interfere with the immunogenic properties of the fusion cells.

CD4-Positive T-Lymphocytes↗

PubMed2005

Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice.

Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2-/- knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2-/- KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopamine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2-/- KO mice. The mGluR2-/- KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.

Animals↗

PubMed2005

Induction of impaired antitumor immunity by fusion of MHC class II-deficient dendritic cells with tumor cells.

To dissect the role of Ag presentation through MHC class I and/or II pathways by dendritic cell (DC)-tumor fusion cells, we have created various types of DC-tumor fusion cells by alternating fusion cell partners. Fusions of MC38/MUC1 carcinoma cells with DC from wild-type (WT-DC), MHC class I knockout (IKO-DC), class II knockout (IIKO-DC), or class I and II knockout (I/IIKO-DC) mice created WTDC-fusion cells (FC), IKO-FC, IIKO-FC, and I/IIKO-FC, respectively. MHC class II- and MUC1-positive fusion cells were constructed by fusion of B16/MUC1 melanoma cells with IKO-DC (IKO/B16-FC). Immunization of MUC1 transgenic mice with 5 x 10(5) WTDC-FC, IKO-FC, IIKO-FC, or I/IIKO-FC provided 100, 91.7, 61.5, and 15.4% protection, respectively, against tumor challenge with MC38/MUC1 cells. In contrast, all mice immunized with irradiated MC38/MUC1 tumor cells or WT-DC developed tumors. One group of mice was immunized with 5 x 10(5) IKO/B16-FC and then challenged with B16/Ia(+)/MUC1 on one flank and MC38/MUC1 on the other flank. Immunization of these mice with IKO/B16-FC resulted in 100 and 78.6% protection against B16/Ia(+)/MUC1 and MC38/MUC1 tumor challenge, respectively. The antitumor immunity induced by immunization with IKO/B16-FC was able to inhibit the growth of MHC class II-negative tumor. In addition, in vivo results correlated with the induction of Ag-specific CTL. Collectively, the data indicate that MHC class II Ag presentation targeting activation of CD4 T cells is indispensable for antitumor immunity.

Animals↗

PubMed2005

Esophagobronchial fistula in a patient with Behçet's disease: report of a case.

Esophageal involvement in Behçet's disease is generally considered to be very uncommon. So far, six cases of esophageal ulcers associated with perforation, penetration, or fistula in Behçet's disease have been described in the English literature. This report describes esophagobronchial fistula in a patient with intestinal Behçet's disease. A 62-year-old man was transferred to our hospital for peritonitis due to a small intestinal perforation after an appendectomy. At the age of 14 years he had had recurrent oral ulcers. Ulcerations of the ileum and epididymitis were found, and a pathological examination revealed nonspecific inflammation. Furthermore, an esophageal ulcer with esophagobronchial fistula was diagnosed. The fistula required not only endoscopic treatment but also surgical intervention. The patient's clinical features were consistent with the active phase of intestinal Behçet's disease. The symptoms gradually resolved without any treatment. Four years after remission, however, the symptoms recurred with gastrointestinal hemorrhage and polyarthritis. In the ileocolic region, punch-out ulcerations were noted. The clinical history and features led to a diagnosis of Behçet's disease associated with recurrent gastrointestinal ulcerations. Steroid therapy (prednisolone, 20 mg daily) was started, and led to a rapid resolution of the symptoms. The patient is now being followed up as an outpatient while receiving prednisolone (10 mg per day), without complaint of any gastrointestinal symptoms.

Adrenal Cortex Hormones↗

PubMed2005

Excellent response of chemotherapy-resistant B-cell-type chronic lymphocytic leukemia with meningeal involvement to rituximab.

A 70-year-old woman was diagnosed with B-cell-type chronic lymphocytic leukemia (B-CLL) in May 2001. Initial white blood cell (WBC) count was 37 x 10(9)/l and most of the cells were mature small lymphocytes. Surface antigen analysis of these lymphocytes revealed positive reactions for CD19, 20, 25, 5, and lambda-light chain. Despite her Rai stage-0 status, various treatments were ineffective, including cyclophosphamide; fludarabine; 6-mercaptopurine; a combination of vincristine, cyclophosphamide, prednisolone, and adriamycin; and etoposide. Her WBC count increased, ranging from 150 to 450 x 10(9)/l, with marked splenomegaly, and symptoms of meningitis, such as headache, ophthalmalgia, hearing disturbance, and abnormal behavior, being manifested. The WBC count in the cerebrospinal fluid was elevated to 134/microl. The surface phenotype of these cells was identical to that of circulating lymphocytes, indicating meningeal involvement of leukemia, a rare complication in B-CLL. At the time of this WBC elevation, 24% of circulating lymphocytes had prominent nucleoli, indicating progression of the disease to CLL/prolymphocytic leukemia. Her symptoms disappeared after repeated intrathecal injections of methotrexate and dexamethazone. After four courses of treatment of the refractory B-CLL with rituximab, an anti-CD20 monoclonal antibody, the WBC count returned to normal levels and the splenomegaly disappeared. She is currently well, with sustained remission, as of April 2004.

Aged↗

PubMed2005

Shear bond strength of resin composite to magnetic Fe-Pt alloy.

STATEMENT OF PROBLEM: It is important to obtain strong adhesion between resin composite material and magnetic Fe-Pt alloy for fabrication of an indirect veneered crown. However, little is known about the bond strength between these materials. PURPOSE: This study evaluated the bond strength of resin composite to magnetic Fe-Pt alloy, using 4 adhesive metal primers. MATERIAL AND METHODS: Seventy disk-shaped patterns (7.5 mm in diameter, 2.0 mm thick) were cast from a custom-made Fe-Pt ingot using a high-frequency centrifugal casting machine. After the bonding surfaces were airborne-particle abraded with 50 microm Al2O3, specimens were divided into groups (n=7) and primed with either Metal Primer II (MP), Meta Fast Bonding Liner (BL), New Meta Color INFIS Opaque Primer (IN), or Epricord Opaque Primer (EP). Nonprimed specimens served as controls (n=7). A resin composite (New Meta Color INFIS) was then applied to all specimens and polymerized. After the specimens were immersed in 37 degrees C water for 24 hours or thermal cycled at 4 degrees C to 60 degrees C with a 1-minute dwell time of up to 10,000 cycles, the shear bond strengths (MPa) were measured using a universal testing machine at a crosshead speed of 0.5 mm/min. The data were statistically analyzed by a 2-way analysis of variance and the Scheffe test (alpha=.05). RESULTS: Although IN had the lowest strength, there were no significant differences in bond strengths of the other 3 primers (MP, BL, and EP) before thermal cycling. The bond strengths of MP and EP were slightly altered by thermal cycling (P >.05); however, BL and IN underwent a significant decrease (P <.05). CONCLUSION: The results of this in vitro study indicate that MP and EP provide superior long-term shear strength when bonding the resin composite evaluated to Fe-Pt alloy.

Composite Resins↗

PubMed2005

Secoiridoid glucosides from Strychnos spinosa.

Three new secoiridoid glucosides, stryspinoside (1) and strychosides A (2) and B (3), were isolated, together with 23 known compounds, from the dried branches of Strychnos spinosa. The structures of the new compounds were determined by spectroscopic means.

Glucosides↗

PubMed2005

Creation of a cholesteatoma model using three-dimensional cultured skin equivalents.

OBJECTIVES/HYPOTHESIS: Recent years have seen success in establishing methods for cell culture that lead to the creation of a three-dimensional tissue architecture, and this represents a great advance for the ability to carry out research in vitro. Accordingly, the present studies were carried out with the objective of using three-dimensional cultured skin equivalents for the in vitro creation of a model of middle ear cholesteatoma, something that has heretofore been considered to be very difficult. STUDY DESIGN: A cholesteatoma model was created in vitro, and discussion is presented regarding the immigration theory and the retraction theory that have been proposed as explanations of the causation of cholesteatoma. METHODS: Cultured skin equivalents were prepared, followed by creation of an epidermal and dermal defect in them. Then, the changes in the epidermis were investigated histologically. In addition, immunohistochemical studies were performed with regard to the effects exerted on the epidermis when the skin equivalents were cultured in a retracted state. RESULTS: It was confirmed that, as a result of the defect in the epidermis and dermis of the cultured skin equivalents, the epidermis at the edge of the defective site migrated subepidermally, and a stratified structure was formed. On the other hand, the retraction of the epidermis and dermis exerted almost no effect on the epidermal cells themselves. CONCLUSIONS: These results lend credence to the immigration theory as an explanation of the growth of the epidermis from the defective site. Conversely, it was surmised that the retraction theory requires some other factors in addition to retraction.

Biopsy, Needle↗

PubMed2005

Joint properties of cast Fe-Pt magnetic alloy laser-welded to Co-Cr alloy.

This study investigated the joint properties of Fe-Pt alloy laser-welded to Co-Cr alloy. Cast plates (0.5 x 3.0 x 10 mm) were prepared with Fe-Pt and Co-Cr alloys. Fe-Pt plates were butted against Co-Cr plates and laser-welded using Nd:YAG laser. Control and homogeneously welded specimens were also prepared. Laser welding was performed with and without argon shielding. Tensile testing was conducted, and both fracture force (Ff: N) and elongation (El: %) were recorded. There were no differences in the Ff value between the specimens with and without argon shielding for the welded Fe-Pt/Co-Cr. Lower Ff value of the welded specimen was obtained in the order of Fe-Pt alloy < Fe-Pt/Co-Cr < Co-Cr alloy. The results indicated that Fe-Pt welded to Co-Cr had Ff values between the values of homogeneously welded Fe-Pt and Co-Cr alloys. Argon shielding, on the other hand, had no effect on the weld strength between Fe-Pt and Co-Cr alloys.

Argon↗