• Development and Reproduction
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• v.12 no.1
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• pp.97-105
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• 2008

Vinclozolin (VCZ) is a systemic fungicide commonly used in fruits, vegetables and the wine industry. VCZ and its metabolites, butenoic acid (M1) and enanilide (M2) derivatives, act as anti-androgens through actions on the androgen receptor. Although there is growing body of evidence that VCZ's action as an endocrine disrupting chemical (EDC) in male reproductive physiology and pathphysiology, no evidence on the VCZ's EDC action in female is available yet. Previously we found that the prepubertal VCZ exposures could effectively delay the onset of puberty in female rats, suggesting the postponed or weakened activities of hypothalamus-pituitary-ovary (H-P-O) reproductive hormonal axis. The present study was performed to examine whether the VCZ administration affects the transcriptional activities of reproductive hormone-related genes in the same animal model. VCZ (10 mg/kg/day) was administered daily from postnatal day 21 (PND 21) through the day when the first vaginal opening (V.O.) was observed. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus and pituitary, total RNAs were extracted and applied to the semiquantitative reverse transcription polymerase chain reaction (RT-PCR). As a result, treatment with VCZ significantly lowered the transcriptional activity of nitric oxide synthase-2 (NOS-2) which is known to adjust gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus (p<0.01). Similarly, the mRNA levels of KiSS-1, G protein-coupled receptor 54 (GPR54) and GnRH were significantly decreased in hypothalamus (p<0.01) from VCZ-treated group. As expected, the transcriptional activities of luteinizing hormone-${\beta}$ (LH-${\beta}$) and follicle stimulating hormone-${\beta}$ (FSH-${\beta}$) in the anterior pituitary from VCZ-treated group were also significantly lower than those from the control group. The present study indicates that(i) the inhibitory effect of VCZ exposure on the onset of puberty in immature female rats could be derived from the reduced transcriptional activities of gonadotropin subunits and their upstream modulators such as GnRH and KiSS-1 in hypothalamus-pituitary neuroendocrine axis, and (ii) these inhibitory effects could be mediated by NO signaling pathway.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.47-62
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• 1981

d-amphetamine이 사람에서 paranoid schizophrenia와 아주 유사한 model psychosis를 일으키며 또한 사람과 실험동물에서 실제 정신분열증에서 뚜렷이 관찰되는 behavioral perservation을 일으킬 수 있음이 관찰되었다. 이에 많은 학자들은 이러한 양상의 행동변화가 정신분열증의 원인 추구에 중요한 의미를 주는 뇌변화를 반영할지도 모른다는 생각에 많은 연구를 거듭하여 왔다. 지금까지는 주로 catecholamine기전에 대하여 집중적 연구가 수행되어져 왔으나 최근에는 d-amphetamine의 약리기전의 일부는 5-HT기전이 차지하고 있으며, 여러 행동변화에는 catecholaimin 보다 5-HT 가 더 중요하게 관계하고 있다는 주장이 나오고 있다. 또한 d-amphetamine은 시험관내에서 MAO 특히 신경전달물질 분해요소인 A type를 가역적으로 억제할 수 있음이 보고되어 많은 흥미를 끌어왔으나 생체내에서의 억제여부는 직접적으로 확인이 되고 있지 않다. 그러나 최근에 Braestrup(1977)과 El Hait(1978)등은 간접적인 방법으로 생체내에서도 억제시킬 수 있음을 보고하고 있다. 이에 저자는 d-amphetamine에 의해 야기되는 행동변화와 그 밑바탕을 이루는 생화학적 기전에 5-HT가 차지하는 역할을 알아보기 위해서 다음의 실험을 시행하였다. 첫째, d-amphetamine의 급성, 만성 투여가 5-HT의 5-HIAA 로의 turnover와 MAO활성도에 어떤 영향을 미치며, 더 나아가서 이 양자사이에 어느 정도 상관관계가 있는지를 알아보기 위해서 d-amphetamine을 투여한 후 시간 경과에 따라서 뇌내 5-HT, 5-HIAA, 5-HT turnover rate와 MAO 활성도를 측정하였다. 둘째, d-amphetamine, 5-HT 합성을 증가시키는 약물과 합성을 억제시키는 약물을 투여하고, 위의 생화학적 실험과 행동관찰을 병합 실시하여 비교분석하였다. 그 결과는 다음과 같다. 1) d-amphetamine (6 mg/kg)을 급성투여시, 뇌내 5-HT함량이 투여 1시간 후에 최고로(대조치의 123%, p<0.001) 증가되다가 이후 감소하며, 5-HIAA 함량은 처음 15분부터 감소하기 시작하다가 30분에 최저로 떨어지며(대조치의 78%, p<0.005) 이후 증가하여 24시간째는 약간 대조치 이상으로 회복되었다. 미토콘드리아 MAO활성도는 1시간째에 최저로 떨어지다가(대조치의 89%, p<0.05)이후 회복하기 시작하여 24시간째에 약간 대조치 이상으로 회복되었다. 5-HT의 turnover rate는 MAO활성도 변화와 거의 같은 변화를 보였다. 2) 만성투여시 (하루 2번, 14일간 투여)는 5-HT 함량, 5-HIAA 함량, MAO 활성도 및 5-HT turnover rate 모두가 중등도로 감소되었다. (각각 대조치의 87%, 69%, 80%, 79%). 3) MAO 활성도와 5-HT turnover rate 사이에는 높은 상관관계가 있었다. (r=0.866, p<0.001, N=94). 4) MAO 활성도의 역동학 실험에서는 대조치에 비해 투여군에서 Km 값은 의미가 있는 증가가 있었으나 $V_{max}$값은 큰 변동이 없었다. 5) d-amphetamine을 급성 투여할때는 sleeping과 lying components는 상당한 감소를 보인 반면, locomotor activity 는 1시간까지는 상당한 증가를 보였으며 용량이 적을수록 더 큰 증가가 있었다. 반면 stereotypy는 1시간까지 용량이 증가할수록 더 큰 증가가 나타나서 locomotor activity에서 stereotypy 의 증가로 이행을 나타내었다. 만성 투여시는 locomotor activity는 점차적인 감소를 보였으나 stereotypy는 점차적인 증가가 나타나서 14일쯤에는 평형에 도달하였다. 6) PCPA 단독 투여군(400 mg/kg, 3번)에 있어서는 5-HT와 5-HIAA 함량의 상당한 감소가 나타났으나 MAO 활성도와 행동에는 큰 변화를 나타내지 않았다. PCPA전 처치군에 있어서도 5-HT와 5-HIAA 함량은 마찬가지로 상당한 감소를 나타내었으나 gnawing, sniffing과 locomotor activity는 더 증가를, stereotyped head weaving, forepaw treading과 hindlimb abduction은 상당한 감소를 나타내었다. 7) L-tryptophan(100 mg/kg)단독 투여시는 5-HT 함량은 약간 증가를 나타내었으나 5-HIAA 함량은 상당한 증가를 보였다. MAO활성도나 행동은 큰 변화없었다. L-tryptophan 전처치군에 있어서는 5-HT 함량은 더 큰 증가를 보였으나, 5-HIaa 함량은 MAO 활성도는 별 변화없었으며 stereotypedlateral head waving, forepaw treading 과 hindlimb abduction은 증가를, locomotor activity, gnawing과 sniffing components는 감소를 나타내었다. 8) d-amphetamine 단독투여, 혹은 L-tryptophan 전처치, PCPA 전처치후 측정한 5-HT 함량과 stereotyped head weaving, forepaw treading, hinilimb abduction components 사이에는 높은 상관관계가 있었다(r=0.789, p<0.001). 반면 5-HT 함량과 locomotor activity, stereotyped gnawing과 sniffing components 사이에는 약한 음성의 상관관계가 있었다. (r=0.554, p <0.005). 이상의 결과로 미루어 볼때 5-HT의 5-HIAA 로의 turnover rate 는 주로 MAO 활성도에 의해서 조절되며 5-HT 기전이 d-amphetamine에 의해서 야기된 여러 행동변화 중 상당한 부분에서 중요한 역할을 하리라고 생각된다.

• The Journal of Korean Academy of Prosthodontics
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• v.45 no.4
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• pp.506-521
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• 2007

Statement of problem: The cumulative success rate of wide implant is still controversial. Some previous reports have shown high success rate, and some other reports shown high failure rate. Purpose: The aim of this study was to analyze, and compare the biomechanics in wide implant system embeded in different width of crestal bone under different occlusal forces by finite element approach. Material and methods: Three-dimensional finite element models were created based on tracing of CT image of second premolar section of mandible with one implant embedded. One standard model (6mm-crestal bone width, 4.0mm implant diameter central position) was created. Varied crestal dimension(4, 6, 8 mm), different diameter of implants(3.3, 4.0, 5.5, 6.0mm), and buccal position implant models were generated. A 100-N vertical(L1) and 30 degree oblique load from lingual(L2) and buccal(L3) direction were applied to the occlusal surface of the crown. The analysis was performed for each load by means of the ANSYS V.9.0 program. Conclusion: 1. In all cases, maximum equivalent stress that applied $30^{\circ}$ oblique load around the alveolar bone crest was larger than that of the vertical load. Especially the equivalent stress that loaded obliquely in buccal side was larger. 2. In study of implant fixture diameter, stress around alveolar bone was decreased with the increase of implant diameter. In the vertical load, as the diameter of implant increased the equivalent stress decreased, but equivalent stress increased in case of the wide implant that have a little cortical bone in the buccal side. In the lateral oblique loading condition, the diameter of implant increased the equivalent stress decreased, but in the buccal oblique load, there was not significant difference between the 5.5mm and 6.0mm as the wide diameter implant. 3. In study of alveolar bone width, equivalent stress was decreased with the increase of alveolar bone width. In the vertical and oblique loading condition, the width of alveolar bone increased 6.0mm the equivalent stress decreased. But in the oblique loading condition, there was not a difference equivalent stress at more than 6.0mm of alveolar bone width. 4. In study of insertion position of implant fixture, even though the insertion position of implant fixture move there was not a difference equivalent stress, but in the case of little cortical bone in the buccal side, value of the equivalent stress was most unfavorable. 5. In all cases, it showed high stress around the top of fixture that contact cortical bone, but there was not a portion on the bottom of fixture that concentrate highly stress and play the role of stress dispersion. These results demonstrated that obtaining the more contact from the bucco-lingual cortical bone by installing wide diameter implant plays an important role in biomechanics.

• Journal of the Korean earth science society
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• v.24 no.5
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• pp.378-392
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• 2003

The purpose of this study is to investigate the depth of earth science teachers' concern over the 7th Science Curriculum and levels of their use of it in reality, using the tools "Concern" and "Levels of use" which are two important tools use in CBAM. The results of the study are as follows. How much concern do the earth science teachers have over the 7th Science Curriculum? There are seven stages (from 0 stage to 6 stage) of teachers' concern over the curriculum. o stage represents teachers' indifference to the curriculum and 98% teachers are placed in this stage. According to the study on teachers' teaching experience, teachers having from 10 to 14 years of teaching experience are the most indifferent to the 7th Science Curriculum, compared to other teachers. Which levels of use of the 7th science curriculum do earth science teachers choose in reality? There are five levels of use (from 1 to 5) of the 7th curriculum. 43.97% of teachers are placed in the 3rd level called "Mechanical level", which represents a teacher-concerned learning method with consideration of learners' response. According to the study on teachers' frequency of level of use in the fields of "Instruction objects, Instruction contents, Instruction methods, Instruction materials and Evaluation.", teachers chose high levels of use in the fields of "Instruction objects and Instruction contents" and low levels of use in the other three fields. What factors are barriers for earth science teachers to perform the 7th Science Curriculum in reality? 80.9% of teachers have trouble performing the 7th Science Curriculum in reality because of too much routine work, official papers, and lack of instructional materials, laboratories, training systems and workshops. The two biggest barriers among the above are routine work and of official papers. According to the study on teachers' teaching experience, teachers having from 0 to years of teaching experience have the most trouble in performing the curriculum in reality, compared to other teachers.

• Journal of Dental Rehabilitation and Applied Science
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• v.24 no.2
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• pp.169-181
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• 2008

The aim of this study was to compare the retention and stability of implant overdenture according to the shape and the number of magnetic attachment. The experimental groups were designed for the number of implants(1, 2, 4) and shape of magnetic attachments(flat, cushion, dome type) resulting in 9 subgroups. 45 attachments were tested attached to $Br{\aa}nemark$ system implants which were planted on a mandibular model. Each attachment was composed of the magnet assembly embedded in a overdenture sample and the abutment keeper screwed into the implants. Dislodging tensile forces were applied to the overdenture samples using an Instron(cross-head speed 50.80mm/min) in 3 directions simulating function: vertical, oblique, and anterior-posterior. The loading was repeated 10 times in each direction for 45 samples. The values of maximum dislodging force of each subgroup were processed statistically using SPSS V. 12.0 at the 0.05 level of significance. The results of this study were as follows: 1. Flat type magnetic overdenture was the most retentive when subjected to vertically directed forces and dome type was the lest retentive when subjected to obliquely directed forces(p<0.05). 2. In case of planting one implant, flat type had a higher vertically retentive force than anterior-posteriorly retentive force. In case of planting two implants, flat type and dome type had a higher vertically retentive force and in case of planting four implants, flat type and cushion type had a higher vertically retentive force than anterior-posteriorly retentive force(p<0.05). 3. The incremental number of dental implant, without regards to the three types of magnetic attachment shapes, showed higher retention of overdenture(p<0.05). From the results, if a patient need much more retention of implant overdenture, flat type magnetic overdenture would be a good treatment. In case of the bruxism where excessive lateral forces are already present, dome type could be expected to produce better results. In case of planting one implant, flat type is more stable than the other shape of magnet and in case of two implant, flat type and dome type are more stable and in case of four implants, flat type and cushion type are more stable. Planting more than two implants and using flat type magnetic attachment would provide better retention and stability of implant overdenture

• Progress in Medical Physics
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• v.26 no.4
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• pp.250-257
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• 2015

Multi-leaf collimator (MLC) systems are frequently used to deliver photon-based radiation, and allow conformal shaping of treatment beams. Many proton beam centers currently make use of aperture and snout systems, which involve use of a snout to shape and focus the proton beam, a brass aperture to modify field shape, and an acrylic compensator to modulate depth. However, it needs a lot of time and cost of preparing treatment, therefore, we developed the manual MLC for solving this problem. This study was carried out with the intent of designing an MLC system as an alternative to an aperture block system. Radio-activation and dose due to primary proton beam leakage and the presence of secondary neutrons were taken into account during these iterations. Analytical calculations were used to study the effects of leaf material on activation. We have fabricated tray model for adoption with a wobbling snout ($30{\times}40cm^2$) system which used uniform scanning beam. We designed the manual MLC and tray and can reduce the cost and time for treatment. After leakage test of new tray, we upgrade the tray with brass and made the safety tool. First, we have tested the radio-activation with usually brass and new brass for new manual MLC. It shows similar behavior and decay trend. In addition, we have measured the leakage test of a gantry with new tray and MLC tray, while we exposed the high energy with full modulation process on film dosimetry. The radiation leakage is less than 1%. From these results, we have developed the design of the tray and upgrade for safety. Through the radio-activation behavior, we figure out the proton beam leakage level of safety, where there detects the secondary particle, including neutron. After developing new design of the tray, it will be able to reduce the time and cost of proton treatment. Finally, we have applied in clinic test with original brass aperture and manual MLC and calculated the gamma index, 99.74% between them.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.619-634
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• 2002

Background : Many inflammatory mediators and collagenases are involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The increase of matrix metalloproteinase-9 (MMP-9, gelatinase-B) produced mainly by inflammatory cells was reported in many ALI models and connective tissue cells. In this study, the expression of MMP-9 in ventilator-induced lung injury (VILI) model and the effects of matrix metalloproteinase inhibitor (MMPI) on VILI were investigated. Methods : Eighteen Sprague-Dawley rats were divided into three groups: low tidal Volume (LVT, 7mL/Kg tidal volume, 3 $cmH_2O$ PEEP, 40/min), high tidal volume (HVT, 30mL/Kg tidal volume, no PEEP, 40/min) and high tidal volume with MMPI (HVT+MMPI) groups. Mechanical ventilation was performed in room air for 2 hours. The 20 mg/Kg of CMT-3 (chemically modified tetracycline-3, 6-demethyl 6-deoxy 4-dedimethylamino tetracycline) was gavaged as MMPI from three days before mechanical ventilation. The degree of lung injury was measured with wet-to-dry weight ratio and acute lung injury score. Expression of MMP-9 was studied by immunohistochemical stain with a mouse monoclonal anti-rat MMP-9 $IgG_1$. Results : In the LVT, HVT and HVT+MMPI groups, the wet-to-dry weight ratio was $4.70{\pm}0.14$, $6.82{\pm}1.28$ and $4.92{\pm}0.98$, respectively. In the HVT group, the ratio was significantly higher than other groups (p<0.05). Acute lung injury score measured by five-point scale was $3.25{\pm}1.17$, $12.83{\pm}1.17$ and $4.67{\pm}0.52$, respectively. The HVT group was significantly damaged by VILI and MMPI protects injuries by mechanical ventilation (p<0.05). Expression of MMP-9 measured by four-point scale was $3.33{\pm}2.07$, $12.17{\pm}2.79$ and $3.60{\pm}1.95$, respectively, which were significantly higher in the HVT group (p<0.05). Conclusion : VILI increases significantly the expression of MMP-9 and MMPI prevents lung injury induced by mechanical ventilation through the inhibition of MMP-9.

• The korean journal of orthodontics
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• v.33 no.3 s.98
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• pp.211-222
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• 2003

The purpose of this study was to determine whether there is an association between disk displacement of the Temporomandibular Joint (TMJ) and dentofacial asymmetry In orthodontic patients. The subjects consisted of 60 female orthodontic patients between the ages of 18 and 38 years (mean age 23.3 years) who had visited the Department of Orthodontics at Seoul National University Dental Hospital from January 2000 to April 2002. On the basis of magnetic resonance imaging (MRI) of their bilateral TMJs, the subjects were divided Into four groups'. bilateral normal group (twenty-one persons); disk displacement of right TMJ group (six persons); disk displacement of left TMJ group (nine persons); and disk displacement of both TMJs group (twenty-four persons) Postero-anterior (PA) cephalograms and diagnostic models which had been taken before orthodontic treatment were measured. In the linear measurements, a line connecting the right and left Latero-Orbitale (Lo) represented the horizontal reference line (H). The vertical reference line (V) was constructed as a line bisecting and running perpendicular to H. One-way analysis of variance (ANOVA) was used to test whether the mean values of measurements between groups were significantly different. In addition, Bonferronil's multiple comparison test was performed at a level of 0.05. The results were as follows; 1 In the diagnostic model analysis, the overjet, nght molar relationship, and left molar relationship were significantly different among the four groups. 2. In the PA cephalometric analysis, differences in the right and left vertical position of the lower first molar and Ag were significantly dissimilar among the four groups. 3. If the disk displacement of TMJ was present on one side, the ipsilateral ramus was shorter, resulting in asymmetry in the vertical position of Ag. This study indicated that dentofacial asymmetry might be related to the disk displacement of TMJ.

• Toxicological Research
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• v.33 no.2
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• Applied Microscopy
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• v.35 no.3
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• pp.135-152
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• 2005

Prefrontal cortex is a psychological and metaphysical cortex, which deals with feeling, memory, planning, attention, personality, etc. And it also integrates above-mentioned events with motor control and locomotor activities. Prefrontal cortex works as a highest CNS center, since the above mentioned functions are very important for one's successful life, and further more they are upgraded every moments through memory and learning. Many of these highest functions are supposed to be generated via forebrain basal nuclei (caudate nucleus, fundus striati nucleus, accumbens septi nucleus, septal nucleus, etc.). In this experiment, prefrontal efferent terminals within basal forebrain nuclei were ultrastructurally studied. Spraque Dawley rats, weighing $250{\sim}300g$ each, were anesthetized and their heads were fixed on the stereotaxic apparatus (experimental model, David Kopf Co.). Rats were incised their scalp, perforated a 3mm-wide hole on the right side of skull at the 11mm anterior point from the frontal O point (Ref. 13, Fig. 1), suctioned out the prefrontal cortex including cortex of the frontal pole, with suction instrument. Two days following the operations, small tissue blocks of basal forebrain nuclei were punched out, fixed in 1% glutaraldehyde-1% paraformaldehyde solution followed by 2% osmium tetroxide solutions. Ultrathin sections were stained with 1% borax-toluidin blue solution, and the stained sections were obserbed with an electron microscope. Degenerating axon terminals were found within all the basal forbrain nuclei. Numbers of degenerated terminals were largest in the caudate nucleus, next in order, in the fundus striati nucleus, in the accumbens septi nucleus, and the least in the septal nucleus. Only axospinous terminals were degenerated within the caudate nucleus and the fundus striati nucleus, and they showed the characters of striatal motor control system. Axodendritic and axospinous terminals were degenerated within the accumbens septi nucleus and the lateral septal nucleus, and they showed the characters of visceral limbic system. Prefrontal role in integrating the limbic system with the striatal system, en route basal forebrain nuclei, was discussed.