• Title/Summary/Keyword: MIT

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Genetical and Pathological Studies on the Mutant Mice as an Animal Model for Deafness Disease

  • Lee, Jeong-Woong;Lee, Eun-Ju;Lee, Hoon-Taek;Chung, Kil-Saeng;Ryoo, Zae-Young
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.48-48
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    • 2001
  • A new neurological mutant has been found in the ICR outbred strain mouse. Affected mice display profound deafness and a head-tossing and bidirectional circling behavior, showing an autosomal recessive mode of inheritance. It was, therefore, named cir/Kr with the gene symbol cir. The auditory tests identified clearly the hearing loss of the cir mice when compared to wild type mice. Pathological studies confirmed the developmental defects in the middle ear, cochlea, cochlear nerve, and semicircular canal areas, which were correlated to the abnormal behavior observed in the cir mice. Thus, cir mice may be useful as a model for studying inner ear abnormalities and deafness. We have constructed a genetic linkage map by positioning 14 microsatellite markers across the (cir) region and intraspecific backcross between cir and C57BL/6J mice. The cir mouse harbors an autosomal recessive mutation on mouse chromosome 9. The cir gene was mapped to a region between D9Mit116 and D9Mit38 Estimated distances between cir and D9Mit116, and between cir and D9Mit38 are 0.7 and 0.2 cM, respectively. The gene in order was defines : centromere-D9Mit182-D9Mit51/D9Mit79/D9Mit310-D9Mit212/D9Mit184-D9Mit116-cir-D9Mit38-D9Mit20-D9Mit243-D9Mit16-D9Mit55/D9Mit125-D9Mit281. The mouse map location of the cir locus appears to be in a region homologous to human 3q21. Our present date suggest that the nearest flanking marker D9Mit38 provides a useful anchor for the isolation of the cir gene in a yeast artificial chromosome contig.

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The Mouse Mutations Circling and Spinner are Allelic

  • Kyoung in Cho;Lee, Eun-Ju;Kim, Myoung-Ok;Kim, Sung-Hyun;Pakr, Jun-Hong;Jung, Boo-Kyung;Kim, Hee-Chul;Sol ha Hwang;Suh, Jun-Gyo
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.90-90
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    • 2003
  • Circling mice were recorded to display profound deafness and a head-tossing and bidirectional circling behavior, showing an autosomal recessive mode of inheritance. In addition, the histological examination of inner ears revealed that the region around organ of Corti, spiral ganglion neurons and outer hair cells showed definite abnormality. On the other hand, a genetic linkage map was constructed in an intraspecific backcross between cir and C57BL/6J mice. The cir gene was mapped to a region between D9Mitl16/D9Mit15 and D9Mit38 on the mouse chromosome 9. Estimated distances between cir and D9Mitl16, and between cir and D9Mit38 are 0.70 $\pm$ 0.40 and 0.23 $\pm$ 0.23 cM, respectively. The markers in order was defined as follows: centromere-D9Mit182- D9Mit51/ D9Mit79/ D9Mit310- D9Mit212/ D9Mit184- D9Mit116/ D9Mit15- cir- D9Mit38- D9Mit20- D9Mit243- D9Mit16- D9Mit55/ D9Mit125- D9Mit281 Based on genetic mapping, we constructed for a YAC contig across cir region. They covered the entire region or cir and cir gene was located on between the lactotransferrin (ltf) and the macrotubule-associated protein (map4). It is known that sr gene is localized in 64cM of mouse chromosome 9. The two mouse were found to be allelic by complementation test. Recently the spinner mouse has been mapped to our cir region, and tmie gene were elucidated. And further study will be needed in circling mouse to prove tmie gene mutaiton.

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Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Pregnant Mouse Model for Evaluating Causal Association with Stillbirth (가습기살균제 CMIT/MIT의 기도 점적투여를 통한 임신마우스의 사산에 대한 영향)

  • Kang, Byoung-Hun;Kim, Min-Sun;Park, Yeong-Chul
    • Journal of Environmental Health Sciences
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    • v.44 no.5
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    • pp.468-479
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    • 2018
  • Objectives: Recently, a report was published that the humidifier disinfectant CMIT/MIT did not cause developmental toxicity and was not detected in systemic circulation as a result of an inhalation toxicity test. Therefore, this study was carried out to investigate any associations between CMIT/MIT exposure and developmental toxicity using the in vivo apical toxicity test method. Methods: Groups of pregnant ICR mice were instilled in the trachea with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot over a period of seven days from days 11 to 17 days post-coitum. For the in vivo apical toxicity test method, an $LD_{50}$-based dose-range finding model was applied to decide the dose range for inducing developmental toxicity. Results: Among the groups of 0, 0.1, 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT, the exposure groups of 0.5 mg and 1.0 ai/kg/day CMIT/MIT were estimated to reflect the thresholds for the stillbirth and death of pregnant mice, respectively. The groups of 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT induced stillbirth rates of 2.57, 10, and 53.8%, respectively. Another exposure group of 0.75 mg ai/kg/day CMIT/MIT did not induce any deaths of pregnant mice and resulted in a stillbirth rate of 8% in only one of six pregnant mice. Conclusions: CMIT/MIT can induce stillbirth in pregnant mice. It was also concluded that CMIT/MIT moves through the pulmonary circulation system and then continues on through systemic circulation and the placenta. There is a possibility of stillbirth and other health causalities in humans beyond the lungs caused by CMIT/MIT exposure.

Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Mouse Model to Evaluate a Causal Association with Death (마우스의 기도 내 점적을 통한 가습기살균제 CMIT/MIT와 사망 간의 원인적 연관성에 관한 연구)

  • Kim, Hayoung;Chung, Yonghyun;Park, Yeongchul
    • Journal of Environmental Health Sciences
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    • v.43 no.4
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    • pp.247-256
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    • 2017
  • Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

Risk Assessment of 5-Chloro-2-Methylisothiazol-3(2H)-One/2-Methylisothiazol-3(2H)-One (CMIT/MIT) Used as a Preservative in Cosmetics

  • Kim, Min Kook;Kim, Kyu-Bong;Lee, Joo Young;Kwack, Seung Jun;Kwon, Yong Chan;Kang, Ji Soo;Kim, Hyung Sik;Lee, Byung-Mu
    • Toxicological Research
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    • v.35 no.2
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    • pp.103-117
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    • 2019
  • The mixture of 5-chloro-2-methylisothiazol-3(2H)-one (CMIT) and 2-methylisothiazol-3(2H)-one (MIT), CMIT/MIT, is a preservative in cosmetics. CMIT/MIT is a highly effective preservative; however, it is also a commonly known skin sensitizer. Therefore, in the present study, a risk assessment for safety management of CMIT/MIT was conducted on products containing 0.0015% of CMIT/MIT, which is the maximum MIT level allowed in current products. The no observed adverse effect level (NOAEL) for CMIT/MIT was 2.8 mg/kg bw/day obtained from a two-generation reproductive toxicity test, and the skin sensitization toxicity standard value for CMIT/MIT, or the no expected sensitization induction level (NESIL), was $1.25{\mu}g/cm^2/day$ in humans. According to a calculation of body exposure to cosmetics use, the systemic exposure dosage (SED) was calculated as 0.00423 mg/kg bw/day when leave-on and rinse-off products were considered. Additionally, the consumer exposure level (CEL) amounted to $0.77512{\mu}g/cm^2/day$ for all representative cosmetics and $0.00584{\mu}g/cm^2/day$ for rinse-off products only. As a result, the non-cancer margin of safety (MOS) was calculated as 633, and CMIT/MIT was determined to be safe when all representative cosmetics were evaluated. In addition, the skin sensitization acceptable exposure level (AEL)/CEL was calculated as 0.00538 for all representative cosmetics and 2.14225 for rinse-off products; thus, CMIT/MIT was considered a skin sensitizer when all representative cosmetics were evaluated. Current regulations indicate that CMIT/MIT can only be used at concentrations 0.0015% or less and is prohibited from use in other cosmetics products. According to the results of this risk assessment, the CMIT/MIT regulatory values currently used in cosmetics are evaluated as appropriate.

Implementation of MIB/MIT in CORBA based Network Management System (CORBA 기반 네트워크 관리 시스템에서 MIB/MIT 구현)

  • Cho, Haeng-Rae;Kim, Chung-Su;Kim, Young-Tak
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.28 no.2B
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    • pp.117-128
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    • 2003
  • The network management becomes more complicated due to the growth of network technology and introduction of a large number of new multimedia services. TINA has appeared as a concept for the advanced network management system platform using the information technology such as distributed processing and object oriented modeling. Since TINA is on the basis of DPE (Distributed Processing Environment), it can manage networks and services for open telecommunications. In this paper, we propose an implementation strategy of the MIB/MIT to federate various CORBA objects in CORBA based network management system implementing TINA DPE. The proposed strategy is novel in the sense that it can support the distribution of MIB/MIT that is well matched with the distributed component architecture of TINA DPE, and it can also support the scoping and filtering services on the MIT using CORBA Naming Service.

Mixture Toxicity of Methylisothiazolinone and Propylene Glycol at a Maximum Concentration for Personal Care Products

  • Park, Juyoung;Lee, Handule;Park, Kwangsik
    • Toxicological Research
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    • v.34 no.4
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    • pp.355-361
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    • 2018
  • Methylisothiazolinone (MIT) has been used in combination with methylchloroisothiazolinone (CMIT) for cosmetic products such as shampoo, body lotion, and skin care products. The mixture of CMIT/MIT has been found to cause allergic contact dermatitis and is thus no longer permitted for use as a preservative in leave-on cosmetics. However, MIT itself was approved as a stand-alone preservative at a maximum concentration of 100 ppm as the toxicity was derived from CMIT rather than MIT. However, in many countries, allergic skin irritation caused by MIT remains a social concern. In this study, skin irritation was assessed for the presence of MIT, propylene glycol, and their mixture using a 3D human skin model $EpiDerm^{TM}$. Although non-diluted MIT causes serious skin toxicity, skin irritation was not observed at a concentration of 100 ppm, the maximum permissible level for cosmetics and personal care products according to European regulations. Propylene glycol, the most widely used vehicle for MIT, did not cause skin irritation in the 3D skin model. The results are expected to provide information for regulatory policies and guidelines on the use of biocides in consumer products.

Effects of Continuous Speech Therapy in Patients with Non-fluent Aphasia Using kMIT (kMIT를 이용한 비유창성 실어증 환자 음성 언어의 치료효과 연구)

  • Lee Ju Hee;Ko Myun Hwan;Kim Hyun Gi;Hong Ki Hwan
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.16 no.2
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    • pp.158-164
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    • 2005
  • Melody intonation therepy (MIT) is to improve the linguistic aspects of the verbal utterance for aphasic patients utilizing the intact right brain. It is applied to the aphasic patients with good comprehension, poor fluency, and little available speech are thought to be ideal candidates. The purpose of the study was to investigate the effects of Korean Melody intonation therapy (kMIT) in patients with non-fluent aphasia. Five male non-fluent aphasic patients were participated in this study. Average ages were 49.9 years old. Each therapy took 45-50minutes once a week for six months. Aphasic Screen lest (RISS) was used to assess language parameter such as Auditory comprehension, oral expression, reading, writing and calculation ability before and after kMIT. Mean of Length Utterance, verbal intelligibility and articulation disorder were assessed also. Computerized Speech Lab was used to assess the acoustic characteristics of aphasic patients before and after kMIT. The results are as follows : 1) Auditory comprehension, oral expression, reading, writing and calculation ability of the subjects increased after UH'. However, only oral expression showed significant difference (p<0.05). 2) Mean of Length Utterance of five patients generally increased after Un. 3) After kMIT, verbal intelligibility increased and showed significant difference (p<0.05). 4) Misarticulation rate generally decreased after m. 5) Voice Onset Time of the alveolar lenis /t/ and velar lenis /k/ gradually decreased after kMIT. 6) However, intonation pattern were increased gradually in yes'no question after kMIT.

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COVID-19 progression towards ARDS: a genome wide study reveals host factors underlying critical COVID-19

  • Shama Mujawar;Gayatri Patil;Srushti Suthar;Tanuja Shendkar;Vaishnavi Gangadhar
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.16.1-16.14
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    • 2023
  • Coronavirus disease 2019 (COVID-19) is a viral infection produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus epidemic, which was declared a global pandemic in March 2020. The World Health Organization has recorded around 43.3 billion cases and 59.4 million casualties to date, posing a severe threat to global health. Severe COVID-19 indicates viral pneumonia caused by the SARS-CoV-2 infections, which can induce fatal consequences, including acute respiratory distress syndrome (ARDS). The purpose of this research is to better understand the COVID-19 and ARDS pathways, as well as to find targeted single nucleotide polymorphism. To accomplish this, we retrieved over 100 patients' samples from the Sequence Read Archive, National Center for Biotechnology Information. These sequences were processed through the Galaxy server next generation sequencing pipeline for variant analysis and then visualized in the Integrative Genomics Viewer, and performed statistical analysis using t-tests and Bonferroni correction, where six major genes were identified as DNAH7, CLUAP1, PPA2, PAPSS1, TLR4, and IFITM3. Furthermore, a complete understanding of the genomes of COVID-19-related ARDS will aid in the early identification and treatment of target proteins. Finally, the discovery of novel therapeutics based on discovered proteins can assist to slow the progression of ARDS and lower fatality rates.