• Title/Summary/Keyword: Blood Deficiency

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Characterization of Bruton's Tyrosine Kinase Genetic Mutations in One Korean X-linked Agammaglobulinemia Family (반성 열성 범저감마글로불린혈증 1가계 3환자의 Bruton's Tyrosine Kinase 유전자 변이 및 임상 양상)

  • Jo, Eun-Kyeong;Song, Chang-Hwa;Park, Jeong-Kyu;Baek, Young-Jong;Rhu, Hye-Young;Lee, Jae-Ho;Hwang, Tai-Ju;Kook, Hoon
    • Clinical and Experimental Pediatrics
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    • v.45 no.2
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    • pp.183-191
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    • 2002
  • Purpose : X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied the cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells from two siblings and one cousin with XLA, as well as additional family members. Methods : Btk protein expression was analyzed by flow cytometry. Isolation of the coding sequence of the Btk gene was performed by amplification using the reverse transcription-polymerase chain reaction(RT-PCR) technique. Sequence alterations were screened by the single-stranded conformation polymorphism(SSCP) method and characterized by standard sequencing protocols. Results : Cytoplasmic expression of Btk protein in monocytes was not detected in three patients with XLA. In addition, Btk protein analysis clearly showed cellular mosaicism in monocytes from four obligate carriers, findings further supported by SSCP. A single base pair mutation(T to C) in Btk-exon three, which encodes the PH domain, was identified in four XLA patients. A diagnostic sequencing analysis was established to detect heterozygotic pattern in 4 carrier females. Furthermore, we found significant clinical heterogeneity in individuals with the same gene mutation. Conclusion : The implicating genetic alteration provided valuable clues to the pathogenesis of XLA in Korea and the flow cytometric analysis was suggested as a useful tool for rapid detection of XLA patients and carriers. The present study has identified a genetic mutation in the Btk coding region and demonstrated heterogeneity in clinical manifestations among patients with the same mutation. A flow cytometric analysis was found to be informative in establishing a deficiency of Btk protein in both patients and carriers and is recommended as a frontline procedure in the molecular diagnosis and work-up of XLA.

Applications of Prescriptions Including Astragali Radix and Angelicae gigantis Radix in Dongeuibogam (동의보감(東醫寶鑑) 중(中) 황기(黃芪)와 당귀(當歸)가 배오(配伍)된 방제(方劑)의 활용(活用)에 대한 고찰(考察))

  • Kwon, Hyun-Kyong;Kook, Yoon-Bum
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.51-58
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    • 2011
  • Objectives : This study was performed to investigate applications of 171 prescriptions including Astragali Radix and Angelicae gigantis Radix in Dongeuibogam. Methods : 171 prescriptions including Astragali Radix and Angelicae gigantis Radix which have been used separately or concurrently in Oriental Medicine for a long time as a treatment for various disease in Dongeuibogam were studied through order of frequency, symptoms, dosages, etc. Results : 1. 27 times(15.79%) prescriptions are recorded in intumescence chapter, 21 times(12.28%) in fatigue chapter, 11 times(6.43%) in women chapter and 9 times(5.26%) in anus chapter, which are arranged in order of frequency. 2. Yin-yang deficiency treat herbs are ranked top, eliminating intumescence methods, bloody stool, discharging blood from one's vagina, yang deficiency treat herbs are ranked in order of frequency among 107 symptoms in prescriptions including Astragali Radix and Angelicae gigantis Radix. 3. The dosages of Astragali Radix which is more used than Angelicae gigantis Radix are ranged from 3 puns:1 pun ~ 2 nyangs:1.5 nyangs. 1 jeon:5 puns is recorded 8 times(14.29%), 2 jeon:1 jeon is 7 times(12.50%), 1 jeon:3 puns and 1 jeon:7 puns are 24 times(11.2%), 1 nyang is 21 times(9.8%), same amount is 11 times(5.1%), 5 pun is 4 times(7.14%) each, 1.5 jeon:5 puns is 3 times(5.36%) used among 56 prescriptions including Astragali Radix and Angelicae gigantis Radix. 4. The dosages of Astragali Radix which is used same amount Angelicae gigantis Radix are ranged from 2.5 puns each ~ 2 nyangs each, 2.5 chons, same amount each. 1 jeon each is recorded 36 times(38.71%), 1 nyang each is 15 times(16.13%), 0.7 jeon each is recorded 12 times(12.90%), 0.5 jeon each is recorded 6 times(6.45%) used among 93 prescriptions including Astragali Radix and Angelicae gigantis Radix. 5. The dosages of Astragali Radix which is less used than Angelicae gigantis Radix are ranged from 3 puns:7 pun ~ 5 nyangs:12 nyangs. 1 jeon:1.5 jeons is recorded 3 times(13.64%), 0.8 jeon:1 jeon and 1 nyang:2 nyangs are 2 times(9.09%) each, the others are 1 time(4.55%) used among 22 prescriptions including Astragali Radix and Angelicae gigantis Radix. 6. The dosages of (Astragali Radix $\gg$ Angelicae gigantis Radix), (Astragali Radix = Angelicae gigantis Radix) and (Astragali Radix $\ll$ Angelicae gigantis Radix) which are recorded by counts (decoction groups: the other groups) are 52:4(92.86%:7.14%), 70:23(75.27%:24.73%), 13:9 (59.09%:40.91%) respectively. 7. The less using dosage of Astragali Radix and Angelicae gigantis Radix has a more percentage of decoctions groups, The more using dosage of Astragali Radix and Angelicae gigantis Radix has a more percentage of the other groups except decoctions. The less using prescriptions have an effects of controling yin and yang, enhancing blood and chi, etc, as a whole. The more using prescriptions as a form of compound powder have an effects in incurableness disease, chronic diseases, etc. Conclusions : The 171 prescriptions including Astragali Radix and Angelicae gigantis Radix in Dongeuibogam are mainly composed of Dangguibohyul-tang, Samool-tang, Sagoonja-tang and Gobangpoong-tang, Gamri-hwan, etc.

A Study on a paradigm of Radix Aconiti(附子) in the treatment of heart-systemic disease(心系疾患) due to heat syndrome(熱證) (심계영역질환(心系領域疾患) 화열증(火熱證)에 사용된 부자(附子)의 활용(活用)에 대한 문헌적(文獻的) 연구(硏究))

  • Lee, Kyung-Ae;Kweon, Jung-Nam;Lee, Won-Chul
    • The Journal of Dong Guk Oriental Medicine
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    • v.6 no.2
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    • pp.145-165
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    • 1998
  • We inquired into the prescription including Radix Aconiti(附子) on the records of the past. According to the role of Radix Aconiti(附子), we can divide into four group. (1) In the case of excess in the upper and deficiency in the lower(上盛下虛), heat in the upper and cold in the lower(上熱下寒), Radix Aconiti(附子) supplies the fire from the gate of life(命門火) and the fire of deficiency type(虛火) is recurred into the origine(根源) by it. (2) In the case that Yang(陽) is kept externally by Yin(陰)-excess in the interior(陰盛格陽), and there is heat syndrome in the exterior with cold syndrome in the interior(裏寒外熱), Radix Aconiti(附子) can remove cold(祛寒) and revitalizes(回陽). (3) In the case of the heat of excess type syndrome(實熱證), Radix Aconiti(附子) treats heat-syndrome(熱證) with heat-clearing(淸熱) drug. (4) In the case of wind-syndrome(風證) and phlegm-syndrome(痰證), Radix Aconiti(附子) supplies the kidney-Yang(元陽) and promotes movement of the other drugs. According to frequency in use of drugs, we can divide into four group. (1) In e case of the fire of deficiency type(虛火), Radix Aconiti(附子) is used with drugs of invigorating-Yin(補陰), invigorating-Yang(補陽) and diuresis(利水), such as Rhizoma rehmanniae(熟地黃), Cortex cinnamomi(肉桂), Fructus comi(山茱萸), Poria, etc. (2) In the case that Yang is kept externally by Yin(陰)-excess in the interior(陰盛格陽), Radix Aconiti(附子) is used with drugs of dispelling cold(祛寒) and revitalization(回陽), such as Rhizoma zingiberis siccatum(乾薑), Radix glycyrrhizae(甘草), Radix ginseng(人蔘), etc. (3) In the case of the heat of excess type syndrome(實熱證), Radix Aconiti(附子) is used with drugs of heat-clearing(淸熱), such as Rhizoma coptidis(黃蓮). (4) In the case of wind-syndrome(風證) and phlegm-syndrome(痰證), Radix Aconiti(附子) is used with drugs of dispersing(發散), invigorating(補氣), enriching the blood(補血), removing the phlegm(去痰), heat-clearing(淸熱). such as Radix oxterici koreani(羌活), Radix ledebouriellae(防風), Radix ginseng(人蔘), Radix angelicae gigantis(當歸), etc. Especially in many of cases, Radix Aconiti(附子) is used with drugs of nourishing-Yin(滋陰), but it is hardly used with drugs of treating middle-jiao energy(中氣).

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The Mechanism of Iron Transport after Intratracheal Instillation of Iron in Rats (랏트의 기관내 Fe 노출후 Fe 이동에 대한 연구)

  • Kwon, Min;Choi, Byung-Sun;Park, Eon-Sub;Chung, Nam-Hyun;Park, Sung-Jo;Lim, Young;Park, Jung-Duck
    • Journal of Preventive Medicine and Public Health
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    • v.37 no.4
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    • pp.329-336
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    • 2004
  • Objectives : Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. Methods : Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. Results : The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. Conclusions : DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.

Effect of Fermented Cirsium japonicum Extract on Testosterone Deficiency Syndrome (엉겅퀴 발효 추출물을 통한 남성 갱년기 증상 개선 효과)

  • Jeong, Byung Seo;Kim, Seong Hoon;Kim, Hyun Pyo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.7
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    • pp.790-800
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    • 2017
  • As men get older, total testosterone levels decline gradually, and concentrations of free and bioavailable testosterone decline sharply with each decade beyond their 30s. Andropause or testosterone deficiency syndrome (TDS) is defined as a decrease in sexual satisfaction or decline in general well-being accompanied by low levels of testosterone in older men. This male climacteric is characterized by nervousness, reduced potency, decreased libido, irritability, fatigue, depression, memory problems, sleep disturbances, and hot flushes. Cirsium japonicum (CJ) is used as a traditional medicine for hemorrhage, blood congestion, and inflammation in Korea. However, there is no report on the efficacy of CJ treatment for TDS. In this study, we observed the mitigating effect of CJ extract (CE) and fermented CJ extract (FCE) on symptoms of TDS. In elderly male rats, total and testosterone levels, hind limbs muscles, forced swimming time, and total and motile sperm counts significantly increased after daily intake of CE and FCE for 6 weeks. In contrast, sex hormone binding globulin, retroperitoneal fat, total serum cholesterol, and triglyceride levels were significantly reduced in CE and FCE groups. However, there was no difference in prostate specific antigen, aspartate aminotransferase, and alanine aminotransferase levels among all groups, which means CE and FCE did not have putative adverse effects. In a cell experiment, we also observed that CE and FCE enhanced expression of genes related to testosterone biosynthesis but reduced genes involved in testosterone conversion. On the whole, these positive effects on TDS were greater in FCE compared to CE. Thus, these results suggest the potential of FCE as a promising natural product for recovering testosterone levels and alleviating TDS.

A Comparative Study of the Oriental and the Occidental Medical Literature on the Etiologies & Treatments for Palmoplantar Hyperhidrosis (수족한(手足汗)의 원인(原因)과 치료법(治療法)에 대한 동(東).서의학적(西醫學的) 고찰(考察))

  • Ko, Young-Chul;Shin, Jo-Young
    • The Journal of Internal Korean Medicine
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    • v.18 no.2
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    • pp.268-295
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    • 1997
  • Sweating is natural phenomenon necessary for the regulation of an individual's body-temperature. The secretion of sweat is mediated by a portion of our vegetative nervous system(the sympathetic nervous system). In some people, this system is working at a very high activity level, far higher than needed to keep a constant temperature. This condition is referred to as hyperhidrosis. Especially excessive sweating of the hands and the feet is palmoplantar hyperhidrosis or volar hyperhidrosis. This is by far the most distressing condition. It was founded that the first important cause of this was emotional factor. The hands are much more exposed in social and prefessional activities than any other part of our body. Many individuals with palmoplantar hyperhidrosis are limited in their choice of proffession, because unable to manipulate materials sensitive to humidity or reluctant to shake hands; some patients arrive to the point to avoid social contact. The occidental medical treatments for palmoplantar hyperhidrosis include application of topical agents(chemical antiperspirants such as aluminum chloride), iontophoresis(treatment with electrical current), or surgery(thoracic sympathectomy). It was reported that the most effective treatment was thoracic sympathectomy. So this study was started to find the easy and effective oriental medical treatments against the occidental medical treatments through the oriental medical literature. The occidental medical idea for palmoplantar hyperhidrosis is only limited in neurologic system, so surgery is the best treatment. But the oriental medical idea for palmoplantar hyperhidrosis is much wider, so the oriental medical causes and treatments for this are able to be veriety. And the oriental medical teatment is freely in treating the patients of palmoplantar hyperhidrosis, because entire idea including pulse, facial color, mental condition, constitution and other symptom exists in the oriental medicine. The results of a bibliographic study of causes and treatments for palmoplantar are as follows; 1. The main causes of pa1moplantar hyperhidrosis are heat in the stomach, damp-heat in the spleen and the stomach, insufficiency of the spleen-qi and the stomach-qi, deficiency of the spleen-yin and the stomach-yin, and the others are the stomach-cold syndrome, stasis of blood and dyspepsia in the stomach, disorder of the liver-qi, deficiency of the heart-yin and the kidney-yin, deficiency of the heart-yang and the kidney-yang, stagnated heat in the liver and the spleen, the lung channel-heat etc. 2. The main methods of medical treatments for palmoplantar hyperhidrosis are clearing out the stomach-heat, eliminating dampness and heat in the spleen and the stomach, invigorating the spleen-qi and the stomach-qi, reinforcing the spleen-yin and the stomach-yin, warming the stomach, relaxing the liver and alleviating of mental depression and tonifying the heart and the kidney etc. 3. The main prescriptions of palmoplantar hyperhidrosis are Taesihotang, Palmultang-kakam, Samyeongbaechusan, Chongbisan, Sasammaekmundongtang, the others are Leejungtang, Hwangkikonjungtang, Seungkitang, Boyumtang, Baekhotang, Chongsimyonjayum, Moyrosan, etc. 4. Local medicine for external use are liquid after boiling alum in water for about 1 or 2 hours, liquid after boiling alum and pueraria root in water and liquid after boiling stragalus root, pueraria root, ledebouriella root and schizonepeta in water, etc. 5. The methods of acupuncture therapy include invigorating Bokyru, Yumkuk and purgating Hapkouk, or invigorating Bokyru, Kihae and purgating Hapkouk, or steadying Hapkouk, Nokung.

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A Critical Evaluation of the Correlation Between Biomarkers of Folate and Vitamin $B_{12}$ in Nutritional Homocysteinemia (엽산과 비타민 $B_{12}$ 결핍에 의한 호모시스테인혈증 흰쥐의 조직내 비타민 지표간의 상관관계 분석)

  • Min, Hye-Sun;Kim, Mi-Sook
    • Journal of Nutrition and Health
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    • v.42 no.5
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    • pp.423-433
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    • 2009
  • Folate and vitamin $B_{12}$ are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin $B_{12}$ deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folatesufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin $B_{12}$-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 ${\pm}$ 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 ${\pm}$ 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 ${\pm}$ 9.6 nmol/L) compared with rats fed FD and FDH (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin $B_{12}$ deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin $B_{12}$ deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.

The Effect of Ecklonia stolonifera Extracts on Blood Flow and Serum Lipid Level in Ovariectomized Rats (곰피 추출물이 난소를 절제한 흰쥐의 혈액 유동성 및 혈중 지질함량에 미치는 영향)

  • Kim, Young-Kyoung;Jeon, Min-Hee;Park, Yong-Soo;Hwang, Hyun-Jung;Lee, Sang-Hyeon;Kim, Sung-Gu;Kim, Yuck-Young;Kim, Mi-Hyang
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1851-1858
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    • 2010
  • Estrogen deficiency in peri- and postmenopausal women results in variety of neurovegetative, psychic and somatic symptoms, and may contribute to severe diseases within the aged female population. Ecklonia stolonifera (ES) is an edible brown algae traditionally used in fishery towns in Far East Asia. This study was performed to investigate the effects of ES extracts on blood flow and serum lipid concentration in ovariectomized rats. Weight-matched female Sprague-Dawley strain rats were assigned to four groups. Three groups were surgically ovariectomized (OVX). The fourth group was sham operated. Rats were randomly assigned to the following groups: sham-operated rats (Sham), ovariectomized control rats (OVX-CON), ovariectomized rats supplemented with ES extract at 50 mg/kg bw/day (OVX-ES50) and ovariectomized rats supplemented with ES extract at 200 mg/kg bw/day (OVX-ES200). Serum total cholesterol and triglyceride contents decreased in the sham group compared to the OVX-CON group. Six weeks feeding of ES extract resulted in a significant (p<0.05) lowering of serum triglyceride and a lowering tendency of total cholesterol level. The level of Hdl-cholesterol in serum increased by supplementation of ES extracts at 50 mg/kg and 200 mg/kg bw/day (p<0.05). Blood passage time of the ES extracts-supplemented group was higher than the OVX-CON group. The ability of platelet aggregation of groups treated with ES extracts was less than that of the OVX-CON group. These results suggest that the beneficial effects of ES extract may be used to possibly improve on the metabolic syndrome of menopausal women.

Characterization of Mutations in Bruton's Tyrosine Kinase(Btk) Gene from Unrelated 3 X-linked Agammaglobulinemia(XLA) Families in Korea (국내 X-관련성 범저감마글로불린혈증 세가족에 대한 Bruton's Tyrosine Kinase 단백질 발현 및 유전자 변이 분석)

  • Song, Chang-Hwa;Jo, Eun-Kyeong;Park, Jeong-Kyu;Kim, Jung-Soo;Hong, Soo-Jong;Lee, Jae-Ho
    • Clinical and Experimental Pediatrics
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    • v.45 no.3
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    • pp.302-310
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    • 2002
  • Purpose : X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells(PBMC) from three XLA families in Korea. Methods : Heparinized venous blood samples were collected from four XLA patients and additional family members in three unrelated XLA families. Mononuclear cells were separated from their blood and the intracellular Btk protein was characterized by a flow cytometry. The mutation analysis was performed using direct sequencing. Results : Cytoplasmic expression of Btk protein in monocytes was not detected in the patients with XLA. We observed a novel deletion and two point mutations within introns(intron 1 and intron 18) resulting in alternative splicings. In XLA family 2, a 980 bp deletion(from intron 9+191 T to intron 10-215 C) including exon 10 was found in patient P2. He was the only sporadic case in this study, because his mother and brother showed a normal Btk expression by flow cytometry. Conclusion : These identified genetic alterations support the molecular heterogeneity of Btk gene in XLA disease. Additionally, by means of flow cytometric analysis, we diagnosed three hypogammaglobulinemia patients as XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.

Effects of Vitamin C on Airway Hyperresponsiveness in Heavy Smokers (흡연자의 기도 과민반응에 대한 비타민 C의 효과)

  • Lee, Sang-Gab;Kim, Ki-Ryang;Eim, Jeong-Ook;Kim, Heung-Up;Lee, Sang-Soo;Chung, Lee-Young;Kim, Hwi-Jong;Lee, Jong-Deog;Hwang, Young-Sil
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.723-735
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    • 1998
  • Background : Vitamin C has been reported to have a role in the decrease of airway hyperresponsiveness in animal models. This data is based on some metabolic actions of vitamin C, such as promotion of histamine degradation, producing more $PGE_2$ than $PGF_{2\alpha}$ in cyclooxygenase pathway, decrease of smooth muscle contraction, and acting as reducing agent of oxidant. It has been also known that heavy smokers have lower blood levels of vitamin C than nonsmokers and this deficiency in heavy smokers have been explained by several mechanisms, such as increased oxidation by oxidants and free radicals, increased biosynthesis of catecholamine and serotonin released by nicotine, and inadequate dietary intake. In this study, We attempted to assess effect of vitamin C on bronchial hyperresponsiveness in heavy smokers who have bronchial hyperresponsiveness and role of vitamin C on bronchial hyperresponsiveness. Method: To assess acute effect of vitamin C on airway hyperresponsiveness, blood sample for vitamin C level and spirometry, methacholine challenge test were done in 17 smokers and 8 nonsmokers, and one hour after oral administration of vitamin C 3 g, blood sample for vitamin C level and spirometry, methacholine challenge test were repeated. To assess chronic effect of vitamin C on airway hyperresponsiveness, after daily administration of vitamin C 1 g for one week in 17 smokers, blood sample for vitamin C level and spirometry, methacholine challenge test were done. To assess role of vitamin C, after oral administration of vitamin C 3 g plus indomethacin 100 mg in 12 of 15 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were done and after oral intake of indomethacin 100 mg in 12 smokers who were reactive to methacholine challenge test, spirometry and methacholine challenge test were repeated. Result: There were no significant differences in whole blood vitamin C levels between smokers($1.17{\pm}0.22$ mg/dL) and nonsmcikers($1.14{\pm}0.19$ mg/dL) (p>0.05). Fifteen of the 17 smokers(88.2%) were reactive to methacholine challenge test and 10 of the 15 smokers who were reactive to methacholine challenge test were less than 8 mg/dL in $PC_{20}FEV-2$, and 7 of the 8 nonsmokers(87.5%) were nonreactive to methacholine challenge test There were significant decrease in bronchial responsiveness after oral administration of vitamin C 3 g in 13 of the 15 smokers who were reactive to methacholine challenge test This significant decrease persisted with maintenance daily administration of 1 g for one week. $PC_{20}FEV-2$ were not correlated to vitamin C levels in smokers. After oral administration of indomethacin 100 mg, significant reduction of bronchial responsiveness that occured after oral administration of vitamin C 3 g in smokers were attenuated. Conclusion: Although there were no significant differences in whole blood vitamin C levels between smokers and nonsmokers. heavy smokers have significant increase in bronchial responsiveness than nonsmokers. This bronchial hyperresponsiveness of heavy smokers can be attenuated by vitamin C supplement. Disappearance of vitamin C effect by indomethacin supplement may suggest that vitamin C exert its effect via alteration of arachidonic acid metabolism.

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