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The Results of Definitive Radiation Therapy and The Analysis of Prognostic Factors for Non-Small Cell Lung Cancer (비소세포성 폐암에서 근치적 방사선치료 성적과 예후인자 분석)

  • Chang, Seung-Hee;Lee, Kyung-Ja;Lee, Soon-Nam
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.409-423
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    • 1998
  • Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

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Radiation Therapy and Chemotherapy after Breast Conserving Surgery for Invasive Breast Cancer: An Intermediate Result (침윤성 유방암에서 유방보존수술 후 방사선치료 및 항암화학 병용치료의 성적 및 위험인자 분석)

  • Lee, Seok-Ho;Choi, Jin-Ho;Lee, Young-Don;Park, Heoung-Kyu;Kim, Hyun-Young;Park, Se-Hoon;Lee, Kyu-Chan
    • Radiation Oncology Journal
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    • v.25 no.1
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    • pp.16-25
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    • 2007
  • [ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

Multiplication of Infectious Flacherie and Densonucleosis Viruses in the Silkworm, Bombyx mori (가잠의 전염성 연화병 및 농핵병 바이러스 증식에 관한 연구)

  • 김근영;강석권
    • Journal of Sericultural and Entomological Science
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    • v.25 no.2
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    • pp.1-31
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    • 1984
  • Flacherie, as one of the most prevalent silkworm diseases, causes severe economic damage to sericultural industry and its pathogens have been proved to be flacherie virus (FV) and densonucleosis virus (DNV). Multiplications of the viruses in the larvae of the silkworm, Bombyx mori, were studied by the sucrose density gradient centrifugation and electron microscopy. The quantitative and qualitative changes of nucleic acids and proteins were investigated from the midgut and hemolymph in the silkworm larvae infected separately with FV and DNV. The histopathological changes of epithelial cells of infected midgut also were examined by an electron microscope. 1. Purified fractions of FV or DNV in a sucrose density gradient centrifugation yielded one homogenous and sharp peak without a shoulder, suggesting no heterogenous materials in the preparation. Electron microscopy also revealed that FV and DNV were spherical particles, 27nm and 21nm in diameter, respectively. 2. Silkworm larvae showed a decrease in body weight on the 6th day and in midgut weight on the 3rd day after inoculation with FV or DNV. 3. DNA content was higher in the midgut when infected with FV or DNV, but the hemolymph of the infected larvae showed no difference during first 6 days after inoculation, after which DNA concentration declined rapidly. 4. RNA synthesis of silkworm larvae infected separately with FV and DNV was stimulated in the midgut, but RNA content was reduced in the hemolymph at the early stage of virus multiplication. At the late stage of virus multiplication, however, it was extremely reduced in both midgut and hemolymph. 5. The concentration of protein in the midgut and hemolymph of silkworm larvae infected separately with FV and DNV showed no difference from that of the healthy larvae at the early stage of virus multiplication, but it was significantly reduced at the late stage of virus multiplication. 6. There was no difference in the electrophoretic patterns of RNAs extracted from the midgut of healthy or virus-infected larvae. 7. The electrophoresis of proteins extracted from the midgut infected with FV or DNV, when carried out on the 1st and 5th day after virus inoculation, showed no difference from that of the healthy larvae. But, there was an additional band with medium motility in the proteins on the 8th day after virus inoculation, while a band with low mobility shown in the proteins of healthy larvae disappeared in the infected larvae. However, a band with high mobility in the healthy larvae was separated into two fractions in the infected larvae. 8. The electrophoretic pattern of hemolymph proteins of the silkworm larvae infected separately with FV and DNV was similar to that of the healthy larvae, but the concentration of hemolymph proteins in the infected larvae was lower than that of the healthy larvae at the late stage. 9. Two types of inclusion bodies were shown by the double staining of pyronin-methyl green in the columnar cell of the midgut on the 8th day after FV inoculation. 10. Electron microscopy of the infected midgut revealed that the 'cytoplasmic wall' of the goblet cell thickened on the 5th day after FV inoculation and several types of the cytopathogenic structures, such as virus$.$specific vesicles, virus particles, linear structures, tubular structures, and high electron-dense matrices were observed in the cytoplasm of the goblet cell. The virus particles were also observed in the microvilli and the structures similar to spherical virus particles were observed around the virus-specific vesicles, suggesting the virus assembly in the cytoplasm. 11. Fluorescence micrograph of the infected midgut stained with acridine orange showed that the nucleus, the site of DNV multiplication in the columnar cell, enlarged on the 5th day after virus inoculation. 12. Electron microscopic examination of DNV infected midgut revealed that the nucleolus of the columnar cell was broken into granules and those granules dispersed into apical region of the nucleus on the 5th day after virus inoculation. On the 8th day after inoculation, it was also observed that the nucleus of the columnar cell was full with the high electron-dense virogenic stroma which were similar to virus particles. These facts suggest that the virogenic stroma were the sites of virus assembly in the process of DNV multiplication.

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Diagnostic Usefulness of Serum Level of Cyfra 21-1, SCC Antigen and CEA in Lung Cancer (폐암에서 혈중 Cyfra 21-1, SCC 항원 및 CEA의 진단적 유용성)

  • Kim, Kyoung-Ah;Lee, Me-Hwa;Koh, Youn-Suck;Kim, Seon-Hee;Lim, Chae-Man;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Moon, Dae-Hyuk
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.846-854
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    • 1995
  • Background: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immunoradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. Method: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay(Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean$\pm$standard deviation. Results: 1) The mean value of Cyfra 21-1 was $18.38{\pm}3.65\;ng/mL$ in the lung cancer and $1.l6{\pm}0.53\;ng/mL$ in the comparison group(p<0.0001). SCC Ag was $3.53{\pm}6.06\;ng/mL$ in the lung cancer and $1.19{\pm}0.5\;ng/mL$ in the comparison group(p<0.01). CEA was $35.03{\pm}13.9\;ng/mL$ in the lung cancer and $2.89{\pm}1.01\;ng/mL$ in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma($31.52{\pm}40.13\;ng/mL$) was higher than that in adenocarcinoma($2.41{\pm}1.34\;ng/mL$)(p<0.0001) and small cell carcinoma($2.15{\pm}2.05\;ng/mL$)(p=0.007). SCC Ag level in squamous cell carcinoma($5.1{\pm}7.68\;ng/mL$) was higher than that in adenocarcinoma($1.36{\pm}0.69\;ng/mL$)(p=0.009) and small cell carcinoma($1.1{\pm}0.24\;ng/mL$) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. Conclusion: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.

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Studies on the morphological variation of plant organs of elongating node-part in rice plant (수도 신장 절위 경엽의 형태변이에 관한 연구)

  • 김만수
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.5 no.1
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    • pp.1-35
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    • 1969
  • Attempts were made to obtain the fundamental knowledge on the quantitative constitution status of leaves and stem of elongating node-part, and the relationships between these morphological characteristics along with the nitrogen contents of leaves and grain yield were examined varing application amounts of nitrogen in rice plant. I. The agronomic characteristics of leaves and nodes of elongation node-part (4-node parts from the top of stem) were observed at heading stage with 20 leading rice varieties of Kang Won district. The results are summarized as follows: 1. Leaf area magnitude of the flag and the fourth leaf was smaller than that of the second and the third with the average value of flag leaf 18.61 $cm^2$, the second leaf 21.84 $cm^2$, the third 21.52 $cm^2$ and the fourth 18.56 $cm^2$. The weight of leaf blade showed an isotonic tendency with the magnitude of leaf area with the value of the flag leaf 97.0 mg, the second leaf 117.1 mg, the third 115.4 mg, and the fourth 95.3 mg. The weight of each leaf sheath was remarkably larger at the higher node-part than at the lower node-part of the stem with the value of flag leaf sheath 176.3 mg, the second 163.7 mg, the third 163.4 mg and the fourth 123.9 mg. Accordingly, the total leaf weight of each part was larger at the second and the third leaf than at the first and the fourth. Total plant weight of each part (weight of leaf blade, leaf sheath, and culm) also was larger at the middle node-part. 2. Coefficients of variation for the varietal differences of the morphological characteristics of elongating node-part were 12.75% for the leaf area, 15.29% for the weight of leaf blade, 15.90%, for the weight of leaf sheath, 11.42% for the weight of internode, 15.45% for the leaf weight (leaf blade & leaf sheath) and 13.24% for the straw weight. And these coefficient values of the most characteristics were, on the whole, smaller at the second and the third node-part than at the first and the fourth node-part, but the coefficient value of the internode weight was rather small at the third and fourth node-part. 3. Constitutional ratio of each plant organ to the total plant weight in term of dry matter weight (excluding head and root wight) was 39.2% for the leaf sheath, 34.2% for the culm, 26.6% for the leaf blade. And ocnstitutional ratio of leaf sheath in term of dry matter weight was larger at the higher position in contrast with that of culm. 4. Average weight ration of leaf blade to culm, leaf sheath to culm, leaf blades to sheath and the leaf blades to culm plus leaf sheath were 77.7 %, 114.5%, 67.9% and 36.2%, respectively. With regard to the position of the plant organ, the weight ratio of leaf blade to culm and that of leaf sheath to culm were larger at higher part in contrast with that of leaf blade to leaf sheath. 5. Generally, there founded deep relationships between grain yield and each morphological characteristics of plant organ of elongating node-part as follows; Correlation coefficient between total area of 4 leaves (from flag to the fourth leaf) and grain yield was ${\gamma}$=0.666$^{**}$ In regard to the position of leaves, correlation coefficient values of flag, the second, the third and the fourth leaf were ${\gamma}$=0.659$^{**}$, ${\gamma}$=0.609$^{**}$, ${\gamma}$=0.464$^{*}$ and ${\gamma}$=0.523$^{*}$, respectively. Correlation coefficient between total weight of leaf blades and the grain yield was ${\gamma}$=0.678$^{**}$. In regard to the position of leaves, that of flag leaf was ${\gamma}$=0.691$^{**}$, and ${\gamma}$=0.654$^{**}$ for the second leaf, ${\gamma}$=0.570$^{**}$ for the third, and ${\gamma}$=0.544$^{**}$ for the fourth. Correlation between the weight of leaves (blade weight plus sheath weight) and the grain yield showed similar values. In the relationship between plant weight and grain yield there also was significant correlation, but with highly significant value only for the first node-part. There appeared correlation between total weight of leaf sheath and grain yield with the value of ${\gamma}$=0.572$^{**}$ and in regard to the position of each leaf sheath the values were ${\gamma}$=0.623$^{**}$ for the flag leaf, ${\gamma}$=0.486$^{**}$ for the second leaf, ${\gamma}$=0.513$^{**}$ for the third, ${\gamma}$=0.450$^{**}$ for the fourth. However, there was no significant correlation between culm weight and grain yield. 6. With respect to in gain yield, varietal differences in magnitude of leaf area, weight of leaf blade, leaf weight per unit area, weight of leaf sheath, culm weight, total leaf and stem weight were larger in the case of high yielding varieties and decreased in accordance with decreasing yield. And this tendency also was shown in the varietal differences of magnitude of each part. Variation in magnitude of each part for the leaf area, weight of leaf blade, culm weight was significantly small in high yielding varieties compared to low yielding varieties. 7. Plant constitutional ratio of each organ of the elongating node-part in term of weight magnitnde varied to som extent according to varieties indicating leaf blade 27.6%, leaf sheath 39.5%, culm 32.9% in the case of high yielding varieties, leaf blade 25.5%, leaf sheath 38.1%, culm 36.4% in the case of low yielding varieties, and medium yielding varieties showed intermadiate values. 8. Far higher values of the weight ration of leaf blade to culm and leaf sheath to culm were given to the high yielding varieties compared to low yielding varieties. And medium yielding varieties showed intermadiate values. II. Effects of application rate of nitrogen on the morphological characteristics of the elongating node-part, nitrogen content of leaf blade, and their relation with the grain yield of the rice were observed with 3 rice varieties; Shin No.2, Shirogane, and Jinheung varying application amounts of nitrogen as 8kg, 12kg and 16kg per 10 are. 1. As for the variation of morphological magnitude s affected by the amounts of nitrogen application, total leaf area (4 leaves from the flag leaf) increased to 16.5% at 12kg N plot, and about 30% at 16kg N polt compared to 8kg N plot and total weight of leaf blade also increased to similar extent, respectively, in contrast with weight of leaf sheath increasing 4.9% and 7.8%, respectively. However, the weight of culm decreased to 1.5% and 11.2%at the 12kg N plot and 16kg N plot, respectively, and these decreasing rate was noted at the nodes of lower part. 2. As for the verietal differences in variation of morphological magnitude as affected by the amount of nitrogen fertilization, leaf area coefficient value of variation of the total leaf area was 15.40% for Shin No. 2, 12.87% for Shirogane, and 10.99% for Jinheung. With respect to the position of nodes, the largest variation of leaf blade magnitude was observed at the fourth for Shin No. 2, the second for Shirogan, and flag leaf for Jinheung. And there also was an isotonic varietal difference in the weight of leaf blade. Variation in total culm weight showed varietal differences with the coefficient value of 7.72% for Shin No.2, 12.11% for Shirogane, and 0.94% for Jinheung. There also was varietal differences in the variation according to the position of nodes. 3. Variation of each elongating node-part related to the fertilization amount decreased with the increase of fertilization amount in the items of leaf area, weight of leaf sheath, culm weight, but weight of leaf sheath varied more at heavier fertilization than at others. 4. Constitutional ratio of each organ excluding head also varied with fertilization amount; constitutional ratio of leaf blade increased much with the increasing amount of fertilization in contrast with the response of culm eight. However, constitutional ration of the weight of leaf sheath was not much affected. 5. Lower value of the ration of leaf blade to culm was given to the 8kg N per 10 are plot, and the ratio of leaf blade to leaf sheath decreased with the increasing amount of fertilization in contrast with the increase in the ratio of leaf sheath to culm. however, the ration of leaf blade to culm plus leaf sheath decreased. 6. With the increase of nitrogen fertilization, leaf area, weight of leaf blade and leaf sheath increased. Accordingly, grin yield also increased to some extent. It was noted that culm weight was changed inversely to the changes in grain yield, but the degree of this variation varied with varietal characteristics. 7. Nitrogen content of leaves at heading and fruiting stage varied with the fertilization amount, and average nitrogen content of leaves of the varieties used 2.19%, 2.49% and 2.74% at the plot of 8kg N, and 12kg N and 16kg N per 10 are, respectively, at heading time, and 0.80%, 0.92% and 1.03% at each plot at fruiting stage. Thus, nitrogen content of leaves increased much with the increasing amount of fertilization, and higher value was given to the leaves on the higher position of elongating node-part. 8. There also was variation of nitrogen content of leaves in accordance with the varieties. However higher grain yield was obtained from the plants retaining higher nitrogen content in leaves at heading or fruiting stage.

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