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A Case of Hunter Syndrome Diagnosed at 7 Months of Age by Exome Sequencing (엑솜시퀀싱을 통해 생후 7개월에 진단된 헌터증후군)

  • Song, Ari;Lee, Jin Sung;Im, Minji;Park, Hyung Doo;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.18 no.2
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    • pp.62-67
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    • 2018
  • Hunter syndrome, also known as mucopolysaccharidosis Type II (MPS II), is one of the lysosomal storage diseases caused by a lack of the enzyme iduronate 2-sulfatase (I2S). Lack of the I2S enzyme activity leads to accumulation of the glycosaminoglycans (GAG), causing dysfunction of multiple organs and systems. MPS II is an X-linked recessive disease due to mutation of IDS gene located on long arm of the X chromosome (Xq28). To date, more than 350 mutations of IDS gene have been identified in Hunter syndrome. Phenotypes of MPS II are classified as either severe or attenuated depending on the degree of cognitive impairment. Because the phenotype of MPS II is related to the type of mutation, identifying mutations is useful in predicting prognosis. We recently had a case of MPS II diagnosed by exome sequencing in a 7 month old boy with infantile spasm uncontrolled by AED. He was diagnosed with hearing loss at 2 months of age, and he took vigabatrin and prednisolone to control infantile spasms diagnosed at 3 months of age. At 6 months of age, whole exome sequencing was performed to evaluate the infantile spasm and hearing loss in this patient, and the mutation c.851C>T (p.Pro284Leu) inherited from hemizygous mother was revealed. The results of urine Cetylpyridinium Chloride (CPC) precipitation test, which were negative until 8 months of age, were positive from 9 months of age. We report a case of MPS II diagnosed by exome sequencing and treated through enzyme replacement therapy from 9 months after birth.

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First report of Telenomus remus Nixon(Scelionidae), an egg parasitoid of Spodoptera frugiperda(J.E. Smith)(Noctuidae) in Korea and its biological characteristics (한국에서 열대거세미나방 알기생벌 Telenomus remus Nixon (가칭: 밤나방검정알벌)[검정알벌과]의 첫 보고 및 생물적 특성 연구)

  • Jum Rae Cho;Bo Yoon Seo;June Yeol Choi;Gwan Seok Lee;Meeja Seo;Jeong Hwan Kim
    • Korean Journal of Environmental Biology
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    • v.40 no.2
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    • pp.187-198
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    • 2022
  • In this study, Telenomus remus Nixon (Hymenoptera: Scelionidae) was first reported as a natural enemy of the fall armyworm Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) egg collected from corn fields in Korea, and its biological characteristics was studied. Based on morphological and molecular analysis, the parasitoid emerged from S. frugiperda eggs was identified as T. remus. We found that T. remus can attack the eggs of S. frugiperda, Spodoptera litra and Spodoptera exigua under a laboratory condition. The longevity of T. remus female adult was longer than that of male adult. The egg-to-adult period of T. remus was not affected by the host age and sex. T. remus female adult laid at least 1-3 eggs a day to a maximum of 37 or more eggs, and the most oviposited on the 3rd to 4th day after emergence. The host preference for oviposition of T. remus adult was high in the order of S. litura>S. exigua>S. frugiperda. T. remus preferred to parasitize 1- and 2-day-old host egg rather than 3-day-old host egg. When compared to the sex ratio of T. remus progeny, the rate of female progeny was higher at the initiation time of oviposition, while the proportion of male progeny increased significantly with female adult age, especially after 8-day-old adult. This information may be useful for improving T. remus mass rearing system and developing a biological control program to control S. frugiperda.

Analysis of Urinary Mass Screening for Elementary, Middle and High School Children Over a 3-year Period(1995-1997) in Seoul (서울지역내 초.중.고 학생들에 실시된 3년 동안의($1995{\sim}1997$) 집단뇨검사 결과 분석)

  • Kang Ho-Seok;Lee Chong-Guk
    • Childhood Kidney Diseases
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    • v.3 no.2
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    • pp.161-169
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    • 1999
  • Purpose : The urinary mass screening program for the detection of proteinuria in school aged population has been performed in Seoul since 1981. Systematic evaluation in corporation with the Seoul School Health Center for students with proteinuria identified in the mass screening has been performed from 1987. The results of urinary mass screening up to 1994 was reported. I report here the results of urinary mass screening from 1995 to 1997 and compare them with previous results and attempt to reveal the significance of urinary mass screening. Objects and Methods : In the 3-year period between 1995 and 1997, annually about 460,000 students comprising 3 different age groups; 5th grade of elementary school, 2nd grade of middle school and 2nd grade of high school were chosen, corresponding to the approximate ages of 11, 14, and 17 years, respectively. These subjects accounted for 26% of total school aged children in Seoul. The screening program was carried out in 3 steps. The 1st test was performed with dipstick at school and the 2nd at the Seoul School Health Center. Those students who showed proteinuria in the 1st and 2nd tests were referred to the hospital. Laboratory examinations including renal biopsies were performed to those students with pathologic proteinuria to clarify the incipient renal diseases. Results : 1) The prevalence of asymptomatic proteinuria was 0.28% in the 1st test. It peaked at the group of 14 years old as 0.34%, compared with 0.26% at the group of 11 years old and 0.24% at the group of 17 years old. It reached to 0.26% in male and 0.30% in female. 2) 25 percent of those having proteinuria at the first test were positive at the second test. 3) The proportion of patients with proteinuria by 3rd test were as follows; 25% of transient proteinuria, 55% of orthostatic proteinuria, 6% of constant proteinuria, 12% of proteinuria with hematuria, and 2% of transient proteinuria with isolated hematuria. Pathologic proteinuria were totaled as 20%. The prevalence of renal diseases among the age group of 7-18 years old was estimated to be 1.4 per 10,000. 4) Renal biopsy performed on 38 children with proteinuria at the third test revealed IgA nephropathy in 17(44%), focal segmental glomerusclerosis in 5(13%), minimal change disease in 4(11%), membranoproliferative glomeronephritis in 3(8%), $Henoch-Sch\"{o}nlein$ purpura nephritis in 3(8%), and others in 6(16%). Therefore, the prevalence of IgA nephropathy among the age group of 7-18 years old was estimated to be 0.64 per 10,000. 5) The prevalence of chronic renal failure was estimated to be 5.7 per 1 million of 7 to 18 years age group. Conclusions : 1) The prevalence of proteinuria in the first screening test was 0.28% and finally only 5% of them showed the pathologic proteinuria at the third test. 2) The prevalence of IgA nephropathy and chronic renal failure were 0.63 per 10,000 and 5.7 per 1 million, respectively among school-aged children in Seoul.

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Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

Expression of Phospholipase C Isozymes in Human Lung Cancer Tissues (인체 폐암조직에서 Phospholipase C 동위효소의 발현양상)

  • Hwang, Sung-Chul;Mah, Kyung-Ae;Choi, So-Yeon;Oh, Yoon-Jung;Choi, Young-In;Kim, Deog-Ki;Lee, Hyung-Noh;Choi, Young-Hwa;Park, Kwang-Ju;Lee, Yi-Hyeong;Lee, Kyi-Beom;Ha, Mahn-Joon;Bae, Yoon-Su
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.3
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    • pp.310-322
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    • 2000
  • Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

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Clinical Study of Corrosive Injury of the Esophagus (식도부식증의 임상적 고찰)

  • 박철원;송기준;이형석;안경성;김선곤
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1981.05a
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    • pp.5.3-6
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    • 1981
  • There are too many kinds of esophageal corrosive agents, such as sodium hydrochloride, acetic acid, hydrochloric acid, etc. Esophageal burn due to above chemical agents are decreasing recently, but still many patients visited to the hospital because of swallowing corrosive agents for the purpose of suicide or accidentally. Among the treatment of corrosive injury of the esophagus, prevention of esophageal stricture is the key point. Recently various methods are using as the treatment of corrosive esophagitis and prevention of esophageal stricture. 51 cases of corrosive injury of the esophagus who had been admitted and treated at the Dept. of Otolaryngology, Han Yang University Hospital during past 9 years (from May 1972 to Dec. 1980) were evaluated and report the result about age distribution, sex incidence, monthly distribution, cause of swallowing, swallowing agents, arriving time at hospital after swallowing, changes on oral and pharyngeal mucosa, laboratory findings, emergency treatment and treatment during admission, treatment follow up results and complications with review of liter ature. Following results were obtained; 1. Female patients 27 cases (52.9%) were more than male patients 24 cases (47.1%) and its ratio was 1.13 : 1. 2. Age distribution showed predilection for age of 21-30 with 20 cases(39.2%), and 11-20 with 11 cases (21.6%), 31-40 with 7 cases(13.7%), over 50 with 7 cases (13.7%) were following. 3. Monthly distribution showed predilection for March with 8 cases(15.7%), and April, July with 7 cases (13.7%), September with 6 cases(l1.8%), October 5 cases(9.8%) were following. 4. For the purpose of suicide was the most cause of swallowing with 40 cases(78.4%), and accidentally swallowing 11 cases(21.6%). 5. Acetic acid was the most swallowing agent with 24 cases (47.0%), and hydrochloric acid 11 cases (21.5%), lye 8 cases(15.7%), iodine 2 cases(3.9%) were following. 6. Arriving time at the hospital after swallowing showed predilection for within 12 hours with 42 cases (82.4%), and from 12 hours to 24 hours with 4 cases(7.8%) was next. 7. Moderate change with injection and swelling was the prevalent change on oral and pharyngeal mucosa with 20 cases(39.2%) and severe cases with ulceration 18 cases (35.3%), mild cases with injection 10 cases (19.6%) were following. 8. Leukocytosis was seen on 40 cases (78.4%), and increased Hct. was seen 31 cases (60.8%). On urine analysis, 14 cases(27.5%) showed over 1.030 S.G., and proteinuria was seen on 25 cases(49.0%), glycosuria was seen on 5 cases(9.8%) and hematuria was seen on 6 cases(11.8). 9. Gastric lavage was done on 30 cases (58.8%) as emergency treatment and on 3 cases(5.9%) tracheostomy was done for the airway keeping. 10. As methods of treatment during admission, L-tube insertion was done on 50 cases (98.0%), antibiotics was given to 49 cases (96.1%), steroid and antacid were given to 46 cases(90.2%). 11. 36 cases(70.6%) were in favorable condition after proper treatment, but 2 cases (3.9%) were expired during admission, 4 cases (7.8%) showed esophageal stricture in-spite of treatment, and 1 case(2.0%) showed pyloric stenosis. 12. Complications were observed in 8 cases (17.7%). Renal failure (4 cases), aspiration pneumonia (2 cases), upper G-I bleeding (1 cases), and diabetic coma (1 cases) were seen in order of frequency.

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The Variation of Natural Population of Pinus densiflora S. et Z. in Korea (III) -Genetic Variation of the Progeny Originated from Mt. Chu-wang, An-Myon Island and Mt. O-Dae Populations- (소나무 천연집단(天然集團)의 변이(變異)에 관(關)한 연구(硏究)(III) -주왕산(周王山), 안면도(安眠島), 오대산(五臺山) 소나무집단(集團)의 차대(次代)의 유전변이(遺傳變異)-)

  • Yim, Kyong Bin;Kwon, Ki Won
    • Journal of Korean Society of Forest Science
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    • v.32 no.1
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    • pp.36-63
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    • 1976
  • The purpose of this study is to elucidate the genetic variation of the natural forest of Pinus densiflora. Three natural populations of the species, which are considered to be superior quality phenotypically, were selected. The locations and conditions of the populations are shown in table 1 and 2. The morphological traits of tree and needle and some other characteristics were presented already in our first report of this series in which population and family differences according to observed characteristics were statistically analyzed. Twenty trees were sampled from each populations, i.e., 60 trees in total. During the autumn of 1974, matured cones were collected from each tree and open-pollinated seeds were extracted in laboratory. Immediately after cone collection, in closed condition, the morphological characteristics were measured. Seed and seed-wing dimensions were also studied. In the spring of 1975, the seeds were sown in the experimental tree nursery located in Suweon. And in the April of 1976, the 1-0 seedlings were transplanted according to the predetermined experimental design, randomized block design with three replications. Because of cone setting condition. the number of family from which progenies were raised by populations were not equal. The numbers of family were 20 in population 1. 18 in population 2 and 15 in population 3. Then, each randomized block contained seedlings of 53 families from 3 populations. The present paper is mainly concerned with the variation of some characteristics of cone, seed, needle, growth performance of seedlings, and chlorophyll and monoterpene compositions of needles. The results obtained are summerized as follows. 1. The meteorological data obtained by averaging the records of 30 year period, observed from the nearest station to each location of populations, are shown in Fig. 3, 4, and 5. The distributional pattern of monthly precipitation are quite similar among locations. However, the precipitation density on population 2, Seosan area, during growing season is lower as compared to the other two populations. Population 1. Cheong-song area, and population 3, Pyong-chang area, are located in inland, but population 2 in the western seacoast. The differences on the average monthly air temperatures and the average monthly lowest temperatures among populations can hardly be found. 2. Available information on the each mother trees (families) studied, such as age, stem height, diameter at breast height, clear-bole-length, crown conditions and others are shown in table 6,7, and 8. 3. The measurements of fresh cone weight, length and the widest diameter of cone are given in Tab]e 9. All these traits arc concerned with the highly significant population differences and family differences within population. And the population difference was also found in the cone-index, that is, length-diameter ratio. 4. Seed-wing length and seed-wing width showed the population differences, and the family differences were also found in both characteristics. Not discussed in this paper, however, seed-wing colours and their shapes indicate the specificity which is inherent to individual trees as shown in photo 3 on page 50. The colour and shape are fully the expression of genetic make up of mother tree. The little variations on these traits are resulted from this reason. The significant differences among populations and among families were found in those characteristics, such as 1000-seed weight, seed length, seed width, and seed thickness as shown in table 11. As to all these dimensions, the values arc always larger in population 1 which is younger in age than that of the other two. The population differences evaluated by cone, seed and seed-wing sizes could partly be attributed to the growth vigorousity. 5. The values of correlation between the characteristics of cone and seed are presented in table 12. As shown, the positive correlations between cone diameter and seed-wing width were calculated in all populations studied. The correlation between seed-wing length and seed length was significantly positive in population 1 and 3 but not in population 2, that is, the r-value is so small as 0.002. in the latter. The correlation between cone length and seed-wing length was highly significant in population 1, but not in population 2. 6. Differences among progenies in growth performances, such as 1-0 and 1-1 seedling height and root collar diameter were highly singificant among populations as well as families within population(Table 13.) 7. The heritability values in narrow sense of population characteristics were estimated on the basis of variance components. The values based on seedling height at each age stage of 1-1 and 1-0 ranged from 0.146 to 0.288 and the values of root collar diameter from 0.060 to 0.130. (Table 14). These heritability values varied according to characteristics and seedling ages. Here what must be stated is that, for calculation of heritability values, the variance values of population was divided by the variance value of environment (error) and family and population. The present authors want to add the heritability values based on family level in the coming report. It might be considered that if the tree age is increased in furture, the heritability value is supposed to be altered or lowered. Examining the heritability values studied previously by many authors, in pine group at age of 7 to 15, the values of height growth ranged from 0.2 to 0.4 in general. The values we obtained are further below than these. 8. The correlation between seedling growth and seed characteristics were examined and the values resulted are shown in table 16. Contrary to our hypothetical premise of positive correlation between 1-0 seedling height and seed weight, non-significance on it was found. However, 1-0 seedling height correlated positively with seed length. And significant correlations between 1-0 and 1-1 seedling height are calculated. 9. The numbers of stomata row calculated separately by abaxial and adaxial side showed highly significant differences among populations, but not in serration density. On serration density, the differences among families within population were highly significant. (Table 17) A fact must be noted is that the correlation between stomata row on abaxial side and adaxial side was highly significant in all populations. Non-significances of correlation coefficient between progenies and parents regarding to stomata row on abaxial side were shown in all populations studied.(Table 18). 10. The contents of chhlorophyll b of the needle were a little more than that of chlorophyll a irrespective of the populations examined. The differences of chlorophyll a, b and a plus b contents were highly significant but not among families within populations as shown in table 20. The contents of chlorophyll a and b are presented by individual trees of each populations in table 21. 11. The occurrence of monoterpene components was examined by gas liquid chromatography (Shimazu, GC-1C type) to evaluate the population difference. There are some papers reporting the chemical geography of pines basing upon monoterpene composition. The number of populations studied here is not enough to state this problem. The kinds of monoterpene observed in needle were ${\alpha}$-pinene, camphene, ${\beta}$-pinene, myrcene, limonene, ${\beta}$-phellandrene and terpinolene plus two unknowns. In analysis of monoterpene composition, the number of sample trees varied with population, I.e., 18 families for population 1, 15 for population 2 and 11 for population3. (Table 22, 23 and 24). The histograms(Fig. 6) of 7 components of monoterpene by population show noticeably higher percentages of ${\alpha}$-pinene irrespective of population and ${\beta}$-phellandrene in the next order. The minor Pinus densiflora monoterpene composition of camphene, myrcene, limonene and terpinolene made up less than 10 percent of the portion in general. The average coefficients of variation of ${\alpha}$-pinene and ${\beta}$-phellandrene were 11 percent. On the contrary to this, the average coefficients of variation of camphene, limonene and terpinolene varied from 20 to 30 percent. And the significant differences between populaiton were observed only in myrcene and ${\beta}$-phellandrene. (Table 25).

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