Molecular Classification of Colorectal Cancers and Clinical Application / 대한소화기학회지

The molecular genetics of colorectal cancers (CRCs) is among the best understood of common human cancers. It is difficult to predict the prognosis and/or to predict chemoresponding in CRC patients. At present, prognosis is based predominantly on the tumor stage and pathological examination of the disease. Molecular classification of CRCs, based on genomics and transcriptomics, proposed that CRCs can be classified into at least three-to-six subtypes, depending on the gene expression pattern, and groups of marker genes representing to each subtype have also been reported. Gene expression-based subtyping is now widely accepted as a relevant source of disease stratification. We reviewed the previous studies on CRC subtyping, international consortium dedicated to large-scale data sharing and analytics recently established four consensus molecular subtypes with distinguishing features. Predictive markers identified in these studies are under investigation and large-scale clinical evaluations of molecular markers are currently in progress.

Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis. MATERIALS/METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS: The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-alpha, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION: These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS.

A Study on Mineral Changes on the Weathering Human Hair after Burial using EDX / 대한법의학회지

This study was undertaken to investigate mineral changes in weathered scalp hair after burial. EDX (energy dispersive X-ray spectroscopy) analysis was performed to measure the presence of minerals on the hair surface. Twelve scalp hairs, buried for 5-40 years, were chosen from deceased individuals buried in tombs in Soha-Ri, Kyonggi-Do, and other regions in Korea. Three normal hairs were used as the control group. EDX data showed that carbon, oxygen, and sulfur were detected in hair collected from all three burial grounds. In contrast, calcium was only detected in hair collected from tombs in Soha-ri. The amounts of calcium and sulfur were found to decrease with time for hair collected from tombs in Soha-ri. Similar results were observed with sodium for hair collected from other regions. These results show region specific mineral detection and a decrease in the concentration of minerals with time. Consequently, it is suggested that changes in minerals concentration in weathered hair could be used as basic data in the field of forensic medicine.

Delayed Long Bone Formation in Hyperthermia-exposed Mouse Embryos / 체질인류학회지

Maternal hyperthermia, which is currently confirmed as one of major causative factors inducing growth retardation, congenital anomalies and abortion, is known to influence normal development of CNS and various organ system. In addition, maternal hyperthermia could induce severe developmental defects including development of the limb. However, it is not clearly identified how maternal hyperthermia affects the expression of chondrogenesis-related proteins in developing limb of mouse. Thus, this study is aimed to investigate the effects of the maternal hyperthermia on the expression of a various proteins in developing upper limb. To elucidate it, ICR mice were used in this study, and the animals were divided into control and heat shock groups. The heat shock treatment was given to embryonic day (ED) 8. The animals were sacrificed on ED 11, 13, 15 and 17, and the humerus were removed. Chondrogenesis-related factors such as FGF8, SOX9 and collagen II were detected on ED 11, 13 and 15 using western blot and immunohistochemistry. Developing humerus on ED 17 was stained with alizarin red S and alcian blue. The expression of FGF8 of heat shock groups was continued even though the development was succeeded. SOX9 expression in heat shock groups was significantly elevated on ED 13 compared to the control embryos. In addition, collagen II expression of heat groups was significantly higher than that of the control group on ED 13 and 15. The results of this study suggest that hyperthermia causes delayed endochondral ossification in long bone through continuous expression of FGF8, SOX9 and collagen II proteins even though the endochondral ossification is succeeded.

Delayed Long Bone Formation in Hyperthermia-exposed Mouse Embryos / 체질인류학회지

Maternal hyperthermia, which is currently confirmed as one of major causative factors inducing growth retardation, congenital anomalies and abortion, is known to influence normal development of CNS and various organ system. In addition, maternal hyperthermia could induce severe developmental defects including development of the limb. However, it is not clearly identified how maternal hyperthermia affects the expression of chondrogenesis-related proteins in developing limb of mouse. Thus, this study is aimed to investigate the effects of the maternal hyperthermia on the expression of a various proteins in developing upper limb. To elucidate it, ICR mice were used in this study, and the animals were divided into control and heat shock groups. The heat shock treatment was given to embryonic day (ED) 8. The animals were sacrificed on ED 11, 13, 15 and 17, and the humerus were removed. Chondrogenesis-related factors such as FGF8, SOX9 and collagen II were detected on ED 11, 13 and 15 using western blot and immunohistochemistry. Developing humerus on ED 17 was stained with alizarin red S and alcian blue. The expression of FGF8 of heat shock groups was continued even though the development was succeeded. SOX9 expression in heat shock groups was significantly elevated on ED 13 compared to the control embryos. In addition, collagen II expression of heat groups was significantly higher than that of the control group on ED 13 and 15. The results of this study suggest that hyperthermia causes delayed endochondral ossification in long bone through continuous expression of FGF8, SOX9 and collagen II proteins even though the endochondral ossification is succeeded.

Exercise training and selenium or a combined treatment ameliorates aberrant expression of glucose and lactate metabolic proteins in skeletal muscle in a rodent model of diabetes

Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, (5 micromol/kg body wt(-1)/day(-1)) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.

The Effects of Hyperthermia on FGF-8 and BMP-4 Expression during Early Odontogenesis in Hsp70 Knock-out Mice Fetuses / 체질인류학회지

During early tooth development, multiple signaling molecules are expressed in the dental lamina and induce the dental mesenchyme. One signal, FGF-8, is expressed in the early dental epithelium, another one, BMP-4, has been shown to induce morphologic changes in dental mesenchyme. Meanwhile, hyperthermic exposure during pregnancy, as one of teratogens, is known to disturbe normal development and induce several congenital anomalies. This study is aimed to investigate the effects of maternal hyperthermia on the expressions of FGF-8 and BMP-4 in early odontogenesis. The pregnant Hsp70 knock-out at gestational day 8 were immersed in 43degrees C water bath until their body core temperature reached at 43degrees C. Thereafter, pregnant mice were given more 5 minutes hyperthermic exposure. Heat-untreated Hsp70 KO mice fetuses were used as the control group. Fetuses were collected at embryonic day (ED) 13, 15 and 17. Developing tooth in the mandible was processed for immunohistochemical study. Tissue sections were immunostained for FGF-8 and BMP-4 and observed with light microscope. The obtained results were as follows: Tooth development in the heat shocked (HS) group is delayed rather than the control group in the given developmental period. FGF-8 immunolocalization in control group at ED 13 was gradually decreased compared to the HS group which showed continuously positive immunoreaction. BMP-4 immunolocalization was detected in dental mesenchyme, however, there was no positive immunoreaction found in HS group. These results suggest that maternal hyperthermia should induce the early odontogenesis, delay the expression of FGF-8 in dental epithelium, and disturbe the expression of BMP-4 in dental mesenchyme. Consequently, hyperthermic exposure during pregnancy affects epithelial-mesenchymal interactions.

Immunohistochemical Study on Early Odontogenesis in Hsp70 Knock-out Mice Fetuses Exposed by Maternal Hyperthermia / 대한해부학회지

To investigate the effects of maternal hyperthermia on early odontogenesis,pregnant Hsp70 knock-out and wild type mice at embryonic day (ED)8.5 were immersed in a 43 degrees C water bath until their core body temperature reached that temperature,and then given a further 5 min of hyperthermia.Untreated Hsp70 WT mice fetuses were used as the control group.Fetuses were collected at EDs 13.5,15.5 and 17.5.Developing teeth in the mandible were processed for histological and immunohistochemical studies.Tissue sections were immunostained for FGF-8 and FGF -4 and observed using light microscopy.In the controls, FGF-8 immunolocalization was observed in cells within the dental lamina and in apically located dental epithelium at ED 13.5.However,a few cells were immunopositive in the heat shocked (HS)group.At EDs 15.5 and 17.5 of the control group,the basal lamina adjacent to the dental pulp showed positive immunostaining.In contrast,most of the dental epithelium was immunopositive at ED 15.5 in the HS group and inner and outer dental epithelial cells were continuously immunopositive by ED 17.5.FGF-4 immunolocalization was found in apical dental epithelium at ED 13.3 in the control group,but no such positive reaction was observed in the HS group.At ED 15.5 in the controls,basal lamina and dental epithelium near the cervical loop were immunopositive.In contrast,early cap-stage teeth had cells near the mouth of the dental bud and cervical loop that were immunopositive to FGF-4 in the HS group.In controls at ED 17.5,cells near the future secondary enamel knot were immunopositive,whereas most of the dental epithelium except for cells in the mouth of the dental lamina was negative in the HS group.Thus,maternal hyperthermia may inhibit normal odontogenesis through sustained production of FGF-8 and downregulation of FGF-4.

Screening of Interleukin-12/interleukin-23 p40 Inducers in Rheumatoid Synovial Fluids by Fluorescence Reporter Mouse System / 체질인류학회지

Although rheumatoid arthritis has been known to be a common autoimmune disease characterized by chronic inflammation mainly evident in diarthrodial joints, its pathogenesis remains to be clarified. In the present study, to investigate the pathogenic signaling system taken place in the rheumatoid joints, we assessed whether synovial fluid obtained from patients with rheumatoid arthritis contains inducers for proinflammatory cytokines such as interleukin (IL)-12 and IL-23. Peritoneal macrophages isolated from IL-12/IL-23 p40-YFP reporter mice were stimulated with synovial fluid, followed by flow cytometry to screen CD11b+ and YFP-expressing cells, reflective of IL-12/IL-23 p40-producing macrophages. The expression levels of Toll-like receptor (TLR)-2 and -4, which have a potential to mediate IL-12/IL- 23 p40 induction, were determined in synovial cells obtained from a patient with rheumatoid arthritis by RT-PCR analyses. One out of 10 synovial fluid from rheumatoid arthritis patients induced IL-12/IL-23 p40 expression, while all of 10 synovial fluid from osteoarthritis patients did not. Synoviocytes constitutively expressed Toll-like receptor (TLR)-2 and -4 which are candidate receptors for IL-12/IL-23 inducers. Upon LPS stimulation, the levels of TLR-2 and -4 were downregulated and upregulated, respectively. Taken together, these results suggest that some patients with rheumatoid arthritis elicit synovitis through TLR-2- and -4-mediated induction of proinflammatory cytokines IL-12 and IL-23.

A Case of the Pancreatic Duct Change after a Long-term Pancreatic Stenting in Pancreas Divisum and the Fine Structural Analysis of Occluded Pancreatic Polyethylene Stent / 대한소화기학회지

The pancreatic duct stenting is now recognized as the treatment option for a number of pancreatic disorders. Although the stent-induced ductal changes may result, there is little information regarding the frequency of these stent-induced changes in chronic pancreatitis. Pancreatic stents may occlude with time, but there is only little information available on the nature of the clogging process. Although a short-term efficacy of endoscopic pancreatic duct stenting has been proved, the long-term efficacy continues to be controversial. The aim of this study was to report a case of chronic pancreatitis with pancreatolith after the incidental long-term pancreatic stenting for 3 years due to a pancreas divisum with acute pancreatitis. Also, this study described the analysis of the ultrastructural changes in the surface of an occluded pancreatic stent. A scanning and transmission electron microscopy showed an amorphous protein matrix in whole stent that arranged as a network in some areas but arranged as the layers in other areas. A variable number of bacteria of mixed species, calcium carbonate or calcium oxalate crystal, round leukocyte were scattered in the protein matrix. The yeast and plant material were seen in some part of the stent as well.

Morphometrics of Arterial Supply for External Pudendal Artery Flap in Koreans / 체질인류학회지

This study was performed to measure the distance of perforating point for superficial and deep external pudendal arteries from pubic tubercle and anterior superior iliac spine, patterns of arterial distribution, and external diameter. Fifty three thighs from 27 Korean cadavers (13 males / 14 females), clinically normal and without deformity, were dissected and standard points were determined as follows: point of pubic tubercle (A) and point of anterior superior iliac spine (B). The obtained results were as follows: 1. The external pudendal artery branched from femoral artery was distributed in the medial thigh. Superficial external pudendal artery is located above the saphenous opening and Deep external pudendal artery is located below the saphenous opening. 2. The saphenous opening were 4.7+/-1.2 cm apart from point A and 10.1+/-1.3 cm from B. 3. The superficial external pudendal artery were 5.2+/-1.2 cm apart from A and 8.9+/-2.1 cm from B. 4. The deep external pudendal artery were 4.7+/-1.1 cm apart from A and 10.8+/-1.3 cm from B. Consequently, the patterns of distribution of superficial and deep external pudendal arteries, obtained in this study, will provide useful anatomical backgrounds for the external pudendal flap surgery in korean.

Effects of Maternal Hyperthermia on the Development of C57/BL6 Strain Hsp70 Knock-out Mice Fetuses / 체질인류학회지

To investigate the effects of maternal hyperthermia on the formation of congenital anomalies, pregnant Hsp70 knock-out and wild type mice at gestational day (GD) 8.5 were immersed in 43degrees C water bath until their body core temperature reached at 43degrees C. Thereafter, pregnant mice were given more 5 minutes hyperthermic exposure. Pregnant mice were killed at GD 15.5, and fetuses were photographed for external appearance analysis. Fetuses with congenital anomalies such as anophthalmia and exencephaly were 72.6% (53 out of 73) in KO group and 28.2% (26 out of 90) in WT group, respectively. Histological findings showed exencephaly, eye abnormalities such as eyeball with retina only or buried eyeball or absence of eye structure, numerous apoptotic cells in the retina and inner ear neuroepithelium, cleft palate, and delayed endochondral ossification. The results of this study suggest that Hsp70 may have a protective function against heat shock.

Effects of Maternal Hyperthermia on the Palatal Mesenchyme Development of Hsp70 Knock-out Mice Fetuses / 체질인류학회지

To investigate the effects of maternal hyperthermia on the development of the palate, pregnant Hsp70 knock-out mice at gestational day (GD) 8.5 were immersed in 43degrees C water bath until their body core temperature reached at 43degrees C. Thereafter, pregnant mice were given more 5 minutes hyperthermic exposure. Heat-untreated Hsp70 WT mice fetuses were used as the control group. Fetuses were collected at embryonic day 13.5, 14.5 and 15.5 (E13.5, E14, 5 and E15.5). Heads followed by removal of the mandible and the tongue were obtained and photographed for palatal development. Developing palates were processed for histological and immunohistochemical studies. Tissue sections were immunostained for TGF-beta2, FGF-8 and fibronectin, and observed with light microscope. The obtained results were as follows: Cleft palate was formed in heat-treated Hsp70 KO fetuses at E14.5 and E15.5. Immunohistochemical findings indicated that TGF-beta2 expression of the experimental fetuses were more delayed than that of the control fetuses. Mesenchyme under the medial edge epithelium (MEE) and cells of MEE showed continuously strong positive TGF-beta2 reactivity at E15.5. FGF-8 was revealed in both of the mesenchyme and the epithelium at the same time. FGF-8 immunoreactivity in the mesenchyme and the epithelium of the heat-treated fetuses showed strong reactivity at E15.5. In the experimental fetuses fibronectin was revealed the mesenchyma and basal lamina at E15.5. Taken together, it is suggested that maternal hyperthermia induces continuous expression of TGF-beta2 and FGF-8 in the mesenchyme and delayed expression of fibronectin. These should affect the normal palatogenesis and result in cleft palate.

Delayed Endochondral Ossification in Hsp70 Knock-out Mice Fetuses due to Maternal Hyperthermia / 대한해부학회지

To investigate the effects of maternal hyperthermia on the endochondral ossification, pregnant Hsp70 knock-out and wild type mice at gestational day (GD)8 were immersed in 43 degree C water bath until their body core temperature reached at 43 degree C. Thereafter, pregnant mice were given more 5 minutes hyperthermic exposure. Fetuses were collected at GD 15 and photographed for external appearance analysis. In addition, heat treated Hsp70 fetuses with external congenital anomalies and heat untreated wild type fetuses were used as experimental and control animals, respectively. Developing humeri at GD 17 were stained with alizarin red S and alcian bue according to the method of Kimmel and Trammell (1981).Developing upper limbs were immunostained for FGF-8, and observed with light and transmission electron microscope. 1.The proportion of average length of the humerus in heat untreated group to heat treated group was 1 :0.58.The proportion of average length of calcified part to average whole length was 1 :0.46 in control and 1 :0.18 in experimental group, respectively. 2.Apical ectodermal ridge was positively reacted to FGF-8 immunohistochemistry in the control group, but not in the experimental group. The humerus of experimental group showed more delayed endochondrial ossification than that of control group. The chondrocytes in the proliferating zone did not react in the experimental group. 3.Collagen fibers were loosely arranged in the experimental group. Mitochondria possessed early staged mitochondrial cristae, i.e.vesicular type in the experimental group. The results of this study suggest that maternal hyperthermia may inhibit the expression of FGF-8 in the developing upper limb, resulting in delayed endochondral bone growth of the humerus.

A study on the stress distribution of the all ceramic crowns according to the cusp angle of the maxillary first premolar using three dimensional finite element method / 대한치과보철학회지

STATEMENT OF PROBLEM: Clinically, maxillary first premolar has a high risk of fracture. This is thought to be caused by the susceptible figure which the maxillary first premolar has. In other words, sharp cusp angles of the premolar is thought to influence this situation. PURPOSE: This study was to know stress distribution of all-ceramic crown according to the cusp angle. MATERIAL AND METHOD: It was manufactured a three dimensional finite element model simplified maxillary first premolar, and then analyzed stress distribution when cusp angle was each 80 degrees, 90 degrees, 100 degrees, 110 degrees and 120 degrees. RESULTS AND CONCLUSION: 1. The von Misses stress showed that stress decreases as cusp angle increases in the central groove of the occlusal surface. 2. It showed that maximum principal stress was centered at the region of the central groove of the occlusal surface and a region which the force was inflicted. And also it appeared high on the lingual and buccal side of finish line. 3. The X axis of normal stress was focused in the central groove of the occlusal surface. The Y axis normal stress appeared high in the central groove of the occlusal surface, buccal and lingual side. 4. The Stress near the finish line showed a low value compared with stress in the region of the central groove of the occlusal surface. 5. It shows that the most dangerous angle for tooth fracture was on 80 degrees of the cusp angle and low on 120 degrees of its.

Distribution of von Willebrand Factor with Angiogenesis in Neonatal Rat Heart / 체질인류학회지

To investigate the process of angiogenesis in the cardiac tissue of neonatal rats, the levels of von Willebrand factor (vWf) produced by endothelial cells were observed. At days 1 to 7 after birth, whole heart obtained from neonatal rats was frozen sectioned, stained with anti-vWf and biotinylated rabbit anti-goat IgG antibodies, followed by immunohistochemical examinations. The results were as follows: 1. At day 1 after birth, extracellular matrix of endocardium and epicardium was stained with anti-vWf at the intermediate level, but that of myocardium was at the low level. 2. At day 2 after birth, a few blood islands were detected. At day 4 after birth, blood island was formed in most parts of heart and extracellular matrix was stained with ant-vWf at the intermediate level. 3. At day 7 after birth, a few blood vessels were formed, and endothelial cells and extracellular matrix was stained with ant-vWf at the intermediate level. These results suggest that mesenchymal cells were differentiated to blood islands and myocardiac cells, which are responsible for the distribution of vWf in extracellular matirx and for angiogenesis.

Death due to glyphosate intoxication / 대한법의학회지

Glyphosate containing herbicides, such as 'Touchdown' or 'Roundup', have been known relatively safe. They have been introduced as substitute for highly toxic paraquat. Till now few researchers have paid their attention for this material, and few data are available concerning this. Recently we experienced seven cases of glyphosate intoxication during past three years. Most of the cases could be regarded as intentional ingestion and accidental intoxication seemed to be quite less compared to paraquat. As there exist technical difficulties for the clarification of the material quantitatively, some cases were disputable concerning the circumstances in which ingestion of the material or death have occurred. Cases were reviewed and several points about this material were discussed.

Anthropometric Study on Neurovascular Supply of the Gracilis Muscle in Korean / 체질인류학회지

Gracilis muscle, the most superficial to the adductor groups of muscles in the thigh, is widely used to make musculo-cutaneous flap because this muscle has several advantages; 1) Removal of the muscle does not elicit any functional deficit, 2) It is easy to make a flap, 3) It is able to make flaps of various sizes in according to the size of the wound. This study demonstrates the characteristics of the arterial supply of the gracilis muscle for flap. Total 102 thighs from 51 Korean cadavers (32 males/ 19 females), clinically normal and without deformity, were dissected and length and width of gracilis muscles were measured. The pattern of distribution of the arteries supplying the muscle were studied, and entering point of each arteries to the muscle were located in according to following point; A: Pubic tubercle, B: Medial condyle of femur and tibia on gracilis muscle. 1. The average width of gracilis muscle were 31.9 +/-8.1 mm. The length of female subjects was significantly shorter than that of male subjects. 2. Arteries supplying the gracilis muscle were obturator artery (11.0%), medial circumflex femoral artery (100%), first muscular branch of femoral artery (100%), second muscular branch of femoral artery (45.2%), third muscular branch of femoral artery (17.8%), and popliteal artery (9.6%). 3. Medial circumflex femoral artery had 1 -10 pedicles and divided into ascending, transverse and descending branches. The existence of ascending branches were 14.8%, the ascending and descending branches were 22.7%, the ascending, transverse and descending branches were 22.7%, the transverse and descending branches were 22.0%, and the only descending branches were 22.0%. 4. The frist muscular branch of femoral artery pierced the gracilis muscle at a distance which represented 61.9 +/-12.8% of the length from A to B. The external diameter were 1.4 +/-0.4 mm. 5. Obturator nerves reached the gracilis muscle at a distance which represented 29.0 +/-7.4% of the length from A to B. The maximum external width and length were 1.0 +/-0.4 mm and 59.7 +/-25.0 mm, respectively. In conclusion, the length and width of the gracilis muscle in Korean were different depending on gender. These data also provides the anatomical characteristics of the arterial supply of the gracilis muscle in Korean in clinical relevance with musculocutaneous flap

Changes in Laminin beta 1 Chain Expression in Renal Cortex by the Intervention with Cilazapril and Losartan on Adriamycin-Induced Nephropathy / 대한해부학회지

Laminin, an extracellular matrix glycoprotein, is distributed in the basement membrane of renal glomerulus. Laminin has been demonstrated to regulate the development and differentiation of glomeruli and play an important role in the filtering function of glomeruli. To address whether laminin beta 1 chain is associated with the pathogenic states of renal injury and recovery, nephropathy were induced by intravenous adriamycin injection and subsequently cured by treatment with antihypertensive drugs, cilazapril (angiotensin-converting enzyme inhibitor, ACEi) and lozartan (angiotensin receptor blockade, ARB), which have been known to be effective on renal protection. The results we obtained were as follows: 1. At 6 and 12 weeks after adriamycin injection, epithelial cells of proximal convoluted tubules exhibited intensive deposition of laminin beta 1 chain reactive gold particles. Cytoplasm of podocytes and mesangial cells in glomeruli showed an increase in the gold particle deposition as compared with that of controls. The mRNA level of laminin beta 1 chain was enhanced in the epithelial cells of proximal convoluted tubules. 2. Following cilazapril administration to adriamycin -induced nephropathy rats, laminin beta 1 chain reactive gold particle deposition was reduced in the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. The level of laminin beta 1 chain transcripts was remarkably decreased in the epithelial cells of proximal convoluted tubules. 3. Following losartan administration to adriamycin -induced nephropathy rats, podocytes and mesangial cells were deposited with reduced number of laminin beta 1 chain reactive gold particles. The laminin beta 1 chain reactive gold particles and level of laminin beta 1 chain mRNA transcripts were remarkably reduced in the epithelial cells of proximal convoluted tubules. 4. Treatment with mixture of cilazapril and losartan to adriamycin -induced nephropathy rat resulted in a decrease in laminin beta 1 chain reactive gold particle deposition within the epithelial cells of proximal convoluted tubules, podocytes, and mesangial cells. Laminin beta 1 chain mRNA expression in the epithelial cells of proximal convoluted tubules nearly disappeared. These results consequently suggest that laminin beta 1 chain may be synthesized within the epithelial cells of proximal convoluted tubules, podocytes and mesangial cells and laminin beta 1 chain may play an important role on tissue recovery of the renal tissues injured by adriamycin.

Electron Microscopic Studies on the Effects of Retinoic Acid on Palatogenesis in Fetal Rats / 체질인류학회지

Retinoic acid (RA) is widely used to treat the dermatologic disorders, such as acne and psoriasis, but its usage is limited because of teratogenic effects. Moreover, it is known that RA induces cleft palate by influencing epithelial differentiation and mesenchymal cells in palatine processes. We studied the ultrastructures of the epithelial and mesenchymal cells in rat palatine shelves treated with RA, in comparison with those of the normal developing rat. In this experiment, pregnant Sprague -Dawley rats were treated with 100 mg/kg of all -trans retinoic acid at day 10 of gestation. Pregnant rats were killed at 14 th and 16 th day of gestation. Fetuses were removed and palatine processes were dissected. The specimen were observed with a transmissiom electron microscope. The results were as follows. 1. Palatine epithelium of control rats was made up of two cell layers at day 14 of gestation, and that of RA treated rats consisted of multicellular layers. At the 16th day of gestation, many apoptotic bodies were observed in triangular area of the palatine epithelium of the control rat. In contrast, apoptotic cells were hardly observed in RA treated rats. 2. Mesenchymal cells of control rats contained cytoplasmic process, oval -shaped nucleus, well -developed rough endoplasmic reticulum, Golgi complex, and mitochondria. RA treated mesenchymal cells showed atrophied cisternae of Golgi complex, rough endoplasmic reticulum with sacculated, fragmented and ribosome detached cisternae, mitochondria with dissolved mitochondrial cristae, and multivesicular body. After RA exposure during palatogenesis, the frequency of apoptotic bodies was low in palatine epithelium, and mesenchymal cells were severely damaged. In conclusion, it is suggested the RA may induce direct cytotoxic effects on mesenchymal cells and influence normal apoptosis process in developing epithelium.