• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.218-227
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• 2006

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.209-216
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• 1999

Purpose : To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). Methods and Materials : We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1990. There were 21 stomach cancer ($35.6\%$), 12 pancreas cancer ($20.3\%$), 15 extrahepatic biliary cancer ($18.0\%$) and 11 another cancer ($18.0\%$). Their pathologies were confirmed in 31 patients ($52.5\%$). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients ($79.7\%$) and abdominal pain in 15 patients ($49.2\%$). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients ($40.6\%$) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients ($54\%$) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto $10.8\~55.8$ Gy (median 37.8 Gy) with palliative aim. Results : Overall median survival duration was $7.80\pm1.15$ months. The response rates of jaundice were $81.8\%$ in PTBO group and $66.7\%$ in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. Conclusion : External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients, Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need luther study consisted with many kinds of treatment methods including new technologies in RT.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.83-90
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• 2008

Purpose: For the first time, a nationwide survey of the Patterns of Care Study(PCS) for the various radiotherapy treatments of esophageal cancer was carried out in South Korea. In order to observe the different parameters, as well as offer a solid cooperative system, we compared the Korean results with those observed in the United States(US) and Japan. Materials and Methods: Two hundreds forty-six esophageal cancer patients from 21 institutions were enrolled in the South Korean study. The patients received radiation theraphy(RT) from 1998 to 1999. In order to compare these results with those from the United States, a published study by Suntharalingam, which included 414 patients[treated by Radiotherapy(RT)] from 59 institutions between 1996 and 1999 was chosen. In order to compare the South Korean with the Japanese data, we choose two different studies. The results published by Gomi were selected as the surgery group, in which 220 esophageal cancer patients were analyzed from 76 facilities. The patients underwent surgery and received RT with or without chemotherapy between 1998 and 2001. The non-surgery group originated from a study by Murakami, in which 385 patients were treated either by RT alone or RT with chemotherapy, but no surgery, between 1999 and 2001. Results: The median age of enrolled patients was highest in the Japanese non-surgery group(71 years old). The gender ratio was approximately 9:1(male:female) in both the Korean and Japanese studies, whereas females made up 23.1% of the study population in the US study. Adenocarcinoma outnumbered squamous cell carcinoma in the US study, whereas squamous cell carcinoma was more prevalent both the Korean and Japanese studies(Korea 96.3%, Japan 98%). An esophagogram, endoscopy, and chest CT scan were the main modalities of diagnostic evaluation used in all three countries. The US and Japan used the abdominal CT scan more frequently than the abdominal ultrasonography. Radiotherapy alone treatment was most rarely used in the US study(9.5%), compared to the Korean(23.2%) and Japanese(39%) studies. The combination of the three modalities(Surgery+RT+Chemotherapy) was performed least often in Korea(11.8%) compared to the Japanese(49.5%) and US(32.8%) studies. Chemotherapy(89%) and chemotherapy with concurrent chemoradiotherapy(97%) was most frequently used in the US study. Fluorouracil(5-FU) and Cisplatin were the most preferred drug treatments used in all three countries. The median radiation dose was 50.4 Gy in the US study, as compared to 55.8 Gy in the Korean study regardless of whether an operation was performed. However, in Japan, different median doses were delivered for the surgery(48 Gy) and non-surgery groups(60 Gy). Conclusion: Although some aspects of the evaluation of esophageal cancer and its various treatment modalities were heterogeneous among the three countries surveyed, we found no remarkable differences in the RT dose or technique, which includes the number of portals and energy beams.

• Journal of Chest Surgery
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• v.41 no.2
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• pp.202-209
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• 2008

Background: The introduction of Drug Eluting Stents (DES) decreased the number of patients referred for coronary artery bypass grafting (CABG). The impact of DES on CABG (Step 1) was studied and compared with the 1-year outcome after CABG with DES (Step 2). Material and Method: Surgical results for patients who underwent off-pump CABG (OPCAB) before the introduction of DES(n=298) were compared with those who underwent OPCAB after the introduction of DES (n=288) (Step 1). Postoperative 30-day and 1-year results were also compared between the patients who underwent percutaneous coronary intervention (PCI) using DES (n=220) and those who underwent OPCAB (n=255) (Step 2). Result: Since the introduction of DES, the ratio of CABG versus PCI decreased. In the CABG group, the number of high risk patients such as elderly patients (age 62 vs. 64, p=0.023), those with chronic renal failure (4% vs. 9%, p=0.021), calcification of the ascending aorta (9% vs. 15%, p=0.043), or frequency of urgent or emergent operations (12% vs. 22%, p=0.002) increased. However, there were no differences in the cardiac death and graft patency rates between the two groups (step 1). During the one-year follow up period, the rate of target vessel revascularization (12.3% vs. 2.4%, p<0.001) and major adverse cardiac events (MACE: death, myocardial infarct, TVR) were higher in the DES than the CABG group (13.6% vs 4.3%) (stage 2). Conclusion: Introduction of DES decreased the number of patients referred for surgery, and increased the comorbidity in patients who underwent CABG. DES increased the rate of target vessel revascularization, and the occurrence of MACE during the 1-year follow-up. However, there was no difference in the incidence of myocardial infarction and cardiac death between the two groups.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.763-773
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• 1996

Background : Behçet's syndrome is a chronic multisystemic disease affecting many organs such as skin, mucosa, eye, joint, central nervous system and blood vessels. Lung involvement occurs in 5% of Behçet's syndrome and is thought to be due to the pulmonary vasculitis leading to thromboembolism, aneurysm and arteriobronchial fistula. Pulmonary vasculitis in Behçet's syndrome is a unique clinical feature, differing from other vasculitis affecting the lung and is one of the major causes of death. Therefore, we examined the incidence, the clinical features, the radioloic findings and the clinical courses of the lung involvement in Behçet's syndrome. Methods: We retrospectively reviewed the medical records and radiologic studies of 10 cases of the lung involvement in Behçet's syndrome diagnosed at Yongdong Severance Hospital and Severance Hospital from 1986 to 1995. We analysed the clinical features, the radiological findings, the treatment modalities and the clinical courses. Results: 1) The incidence of the lung involvement in Behçet's syndrome was 2%(10/487). The male to female ratio was 8 : 2 and the mean age was 34 years. The presenting symptom was hemoptysis in 5 of 10 cases, and massive hemoptysis was noted in 2 cases. Other pulmonary symptoms were cough(6/10), dyspnea(4/10), and chest pain(2/10). Other manifestations were oral ulcers(10/10), genital ulcers(9/10), skin lesions(7/10), and eye lesions(6/10). 2) The laboratory findings were nonspecific. The posteroanterior views of chest radiographies showed multiple infiltrates(6/10), nodular or mass-like opacities(4/10), or normal findings(2/10). The chest CT scans showed multifocal consolidations(6/8), and aneurysms of the pulmonary aneries(4/8). The pulmonary angiographies were performed in 3 cases, and showed pulmonary artery aneurysms in 2 cases. The ventilation-perfusion scans in 2 cases of normal chest x-ray showed multiple mismatched findings. 3) The patients were treated with combination therapy consisting of corticosteroids, cyclophosphamide, and colchicine or anticoagulant agents. Surgical resection was performed in one case with a huge aneurysm. 4) We have followed up nine of ten cases. Three cases are well-being with medical therapy, two cases are severely disabled now and four cases died due to massive hemoptysis, massive pulmonary embolism, or sepsis. Conclusion : Pulmonary vasculitis is a main feature of the lung involvement of Behçet's syndrome, causing hemorrhage, aneurysmal formation, and/or thromboemboism. The lung involvement of Behçet's syndrome is uncommon but is one of the most serious prognostic factors of the disease. Therefore, an aggressive diagnostic work-up for early detection and proper treatment are recommended to improve the clinical course and the survival.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.671-682
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• 1996

Background : Endobronchial tuberculosis is definded as tuberculous infection of the tracheobronchial tree with microbiological and histopathological evidence. Endobronchial tuberculosis has clinical significance due to its sequela of cicatrical stenosis which causes atelectasis, dyspnea and secondary pneumonia and may mimic bronchial asthma and pulmanary malignancy. Method : The authors carried out, retrospectively, a clinical study on 201 patients confirmed with endobronchial tuberculosis who visited the Department of Pulmonary Medicine at Hangyang University Hospital from January 1990 10 April 1996. The following results were obtained. Results: 1) Total 201 parients(l9.5%) were confirmed as endobronchial tuberculosis among 1031 patients who had been undergone flexible bronchofiberscopic examination. The number of male patients were 55 and that of female patients were 146. and the male to female ratio was 1 : 2.7. 2) The age distribution were as follows: there were 61(30.3%) cases in the third decade, 40 cases(19.9%) in the fourth decade, 27 cases(13.4%) in the sixth decade, 21 cases(10.4%) in the fifth decade, 19 cases(9.5%) in the age group between 15 and 19 years, 19 cases(9.5%) in the seventh decade, and 14 cases(7.0%) over 70 years, in decreasing order. 3) The most common symptom, in 192 cases, was cough 74.5%, followed by sputum 55.2%, dyspnea 28.6%, chest discomfort 19.8%, fever 17.2%, hemoptysis 11.5%, in decreasing order, and localized wheezing was heard in 15.6%. 4) In chest X-ray of 189 cases, consolidation was the most frequent finding in 67.7%, followed by collapse 43.9%. cavitary lesion 11.6%, pleural effusion 7.4%, in decreasing order, and there was no abnormal findings in 3.2%. 5) In the 76 pulmanary function tests, a normal pattern was found in 44.7%, restrictive pattern in 39.5 %, obstructive pattern in 11.8%, and combined pattern in 3.9%. 6) Among total 201 patients, bronchoscopy showed caseous pseudomembrane in 70 cases(34.8%), mucosal erythema and edema in 54 cases(26.9%), hyperplastic lesion in 52 cases(25.9%), fibrous s.enosis in 22 cases(10.9%), and erosion or ulcer in 3 cases(1.5%). 7) In total 201 cases, bronchial washing AFB stain was positive in 103 cases(51.2%), bronchial washing culture for tuberculous bacilli in 55 cases(27.4%). In the 99 bronchoscopic biopsies, AFB slain positive in 36.4%. granuloma without AFB stain positive in 13.1%, chronic inflammation only in 36.4%. and non diagnostic biopsy finding in 14.1%. Conclusions : Young female patients, whose cough resistant to genenal antitussive agents, should be evaluated for endobronchial tuberculosis, even with clear chest roentgenogram and negative sputum AFB stain. Furthermore, we would like to emphasize that the bronchoscopic approach is a substantially useful means of making a differential diagnosis of atelectasis in older patients of cancer age. At this time we have to make a standard endoscopic classification of endobronchial tuberculosis, and well designed prospective studies are required to elucidate the effect of combination therapy using antituberculous chemotherapy with steroids on bronchial stenosis in patients with endobronchial tuberculosis.

• Journal of Korean Society of Forest Science
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• v.43 no.1
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• pp.20-30
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• 1979

The purpose of present study is to analyze the genetic variation of natural stand of Pinus densiflora. In 1976 following after the seletion of 1974 and 1975, twenty trees from each of three natural populations of the species were selected and seeds were collected, and the locations and conditions of populations are presented in table 1, 2 and figure 1. Some morphological traits of the populations were already detailed in our fifth report of this series. The morphological traits of cone, seed and seed-wing, and also the growth performances and needle characters of the seedling were observed in the present study according to the previous methods. The results obtained are summarized as follows; 1. The meteorological data obtained by averaging the records of 30 year period(1931~1960) measured from the nearest meteorological station to each population are shown in fig. 2, 3, 4. The distributional patterns of investigated climate factors are generally considered to be similar among the locations. However, the precipitation density during growing season and the air temperature during dormant season on Samchuk area (Pop. 9) were quite different from those of the other areas. 2. The measurements of fresh cone weight, length, diameter and cone index (i.e.: length to diameter ratio) are presented in table 7. As shown in table 7, all these traits except for cone diameter seem to be not significant in population and to be highly significant in family differences within population. 3. The morohological traits of seed and seed-wing are detailed in table 8, 9, and highly significant differences are recognized among the populations and the families within population in seed weight, seed length, seed thickness but not among the populations in the other observed traits. The values of correlation between the characteristics of cone and seed are presented in table 12. As shown, the correlation between cone length and seed wing length, between seed wing width and seed width were significantly positive in population 8 and 9 but in population 7. The positive correlations between seed length and seed width were calculated in all populations studied 4. Significant statistical differences among populations and families within population are observed in the growth performances of 1-0 seedling height of these progenies. But the differences in 1-1 seedling height and root collar diameter are shown only among familes within population. As shown in table 13, the most parts of correlations are not significant statistically between the growth performances of seedling and the seed characters. 5. As shown in table 15, statistical differences are considered to be significant among the populations in stomata row on both sides of the needle but not in serration density. The correlations between progenies and parents are not generally observed in the investigated traits of needle as shown in table 16.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1199-1213
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• 1998

Background : The number of immunocompromised hosts has been increasing steadily and a new pulmonary infiltrate in these patients is a potentially lethal condition which needs rapid diagnosis and treatment. In this study we sought to examine the clinical manifestations, radiologic findings, and therapeutic outcomes of pulmonary mycoses presenting as a new pulmonary infiltrate in immunocompromised hosts. Method : All cases presenting as a new pulmonary infiltrate in immunocompromised hosts and confirmed to be pulmonary mycoses by pathologic examination or by positive culture from a sterile site between October of 1996 and April of 1998 were included in the study and their chart and radiologic findings were retrospectively reviewed. Results : In all, 14 cases of pulmonary mycoses from 13 patients(male : female ratio = 8 : 5, median age 47 yr) were found. Twelve cases were diagnosed as aspergillosis while two were diagnosed as mucormycosis. Major risk factors for fungal infections were chemotherapy for hematologic malignancy(10 cases) and organ transplant recipients(4 cases). Three cases were receiving empirical amphotericin B at the time of appearance of new lung infiltrates. Cases in the hematologic malignancy group had more prominent symptoms : fever(9/10), cough(6/10), sputum(5/10), dyspnea(4/10), chest pain(5/10). Patients in the organ transplant group had minimal symptoms(p<0.05). On simple chest films, all of the cases presented as single or multiple nodules(6/14) or consolidations(8/14). High resolution computed tomograph showed peri-lesional ground glass opacities(14/14), pleural effusions(5/14), and cavitary changes(7/14). Definitive diagnostic methods were as follows : 10 cases underwent minithoracotomy, 2 underwent video-assisted thoracoscopic surgery, 1 underwent percutaneous needle aspiration and 1 case was diagnosed by culture of abscess fluid. All cases received treatment with amphotericin B with 1 case each being treated with liposomal amphotericin B and itraconazole due to renal toxicity. Lung lesion improved in 12 of 14 patient but 4 patients died before completing therapy. Conclusion : When a new lung infiltrate develops presenting either as a nodule or consolidation in a neutropenic patient with hematologic malignancy or in a transplant recipient, you should always consider pulmonary mycoses as one of the differential diagnosis. By performing aggressive work up and early treatment, we may improve prognosis of these patients.

• Journal of Korean Society of Forest Science
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• v.38 no.1
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• pp.33-45
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• 1978

The purpose of present study is to analyze the genetic variation of natural stand of Pinus densiflora. In 1975 following after the selection of 1974, twenty trees from each of three natural populations of the species were selected and their open-pollinated seeds were collected, and the locations and conditions of the populations ate presented in table 1, 2 and figure 1. Some morphological traits of the populations were already detailed in our second report of this series, in which Myong-Ju and Ul-Jin populations were regarded to be superior phenotypically to suweon population. The morphological traits of cone, seed and seed-wing, and also the growth performances and needle characters of the seedling were observed in the present study according to the previous methods. The results obtained are summarized as follows; 1. The meteorological data obtained by averaging the records of 30 year period (1931~1960) measured from the nearest meteorological stations to each population are shown in fig.2, 3, 4. The distributional patterns of investigated climate factors are generally considered to be similar among the locations. However, the precipitation density during growing season and the air temperature during dormant season on Suweon area, population 6, were quite different from those of the other areas. 2. The measurements of fresh cone weight, length, diameter and cone index, i.e., length to diameter ratio are presented in table 7. As shown in table 7, all these traits except for cone diameter seem to be highly significant in population differences and family differences within population. 3. The morphological traits of seed and seed-wing are detailed in table 8, 9, and highly significant differences are recognized among the populations and the families within population in seed-wing length, seed-wing index, seed weight, seed-length and seed index but not among the populations in the other observed traits. The values of correlation coefficient between the characters of cone and seed are given in table 10 and the positive significant correlations can be observed in the most parts of the compared traits. 4. Significant statistical differences among populations and families within population are observed in the growth performances of 1-0 and 1-1 seedling height of these progenies. But the differences in root collar diameter are shown only among families within population. As shown in table 13, the most parts of correlations are not significant statistically between the growth performances of seedling and the seed characters. 5. The number of stomata row on both sides of needle and the serration density were measured in the seedlings from each of the families of the three populations. As shown in table 15, statistical differences are considered to be significant among the populations and among the families within population in serration density but not among the populations in stomata row on both sides of the needle. The results differ from those of the third report of this series. Even if one of the reason seems to be the diversity of selected populations, it could not be confirmed definitely. The correlations between progenies and parents are not generally observed in the investigated traits of needle as shown in table 16.