Pseudoangiomatous Stromal Hyperplasia Presenting as Rapidly Growing Bilateral Breast Enlargement Refractory to Surgical Excision

No abstract available.

A Rare Complication after Latissimus Dorsi Flap Breast Reconstruction: Radial Nerve Palsy

Among autologous breast reconstruction techniques, breast reconstruction using the latissimus dorsi musculocutaneous flap is widely used, offering advantages including the relative simplicity of the procedure and the reliable and consistent vascularity of the flap. Accordingly, more than 500 cases have been performed in the past 8 years at Kyungpook National University Medical Center. This study reports on a rare case involving a radial nerve neuropathy complication which was experienced for the first time at the medical center. The current case demonstrates that in addition to common complications, such as seroma of the donor site and scarring, additional intraoperative complications in areas unrelated to the surgical site can occur, including radial nerve neuropathy in the opposite arm.

Cervicofacial Lymphatic Malformations: A Retrospective Review of 40 Cases

BACKGROUND: Lymphatic malformation (LM) is a form of congenital vascular malformation with a low incidence. Although LM has been studied, no consensus has emerged regarding its cause or treatment. METHODS: In this study, we retrospectively evaluated 40 patients who visited our vascular anomalies center for the treatment of cervicofacial LM, which is a common manifestation of LM. The medical records of patients over a period of 12 years were reviewed and analyzed for commonalities regarding the diagnosis and the results of treatment. RESULTS: Suspected cervicofacial LM was confirmed through imaging studies. No difference in incidence was observed according to sex, and 73% of patients first presented with symptoms before the age of two years. The left side and the V2-V3 area were most commonly affected. No significant differences in incidence were observed among the macrocystic, microcystic, and combined types of LM. A total of 28 out of 36 patients received sclerotherapy as the first choice of treatment, regardless of the type of lesion. Complete resolution was achieved in only 25% of patients. CONCLUSIONS: LM is important to confirm the diagnosis early and to choose an appropriate treatment strategy according to the stage of the disease and each individual patient's symptoms. When treatment is delayed or an incorrect treatment is administered, patient discomfort increases as the lesion gradually spreads. Therefore, more so than is the case for most other diseases, a team approach on a case-by-case basis is important for the accurate and appropriate treatment of LM.

Expression of the p75NTR Neurotrophin Receptor in the Thymic Medullary Epithelial Cells and Interdigitating Dendritic Cells during Rat Thymus Regeneration Following Acute Thymic Involution / 대한해부학회지

The existence of a functional link between the nervous and immune systems has been well established. The present study was to characterize the expression of p75NTR during thymus regeneration from acute involution induced by cyclophosphamide in the rat. Immunohistochemical and double immunofluorescence analyses demonstrated that expression of the p75NTR was decreased in the thymic medullary epithelial cells and interdigitating dendritic cells during thymus regeneration. The presence of p75NTR protein in extracts from the control and regenerating rat thymus was confirmed by western blot. Furthermore, RT-PCR analysis supported these results by demonstrating that thymic extracts contain p75NTR mRNA at lower levels during thymus regeneration. Thus, our results suggest that the p75NTR located on the thymic medullary epithelial cells and interdigitating dendritic cells could play a role in the development of new T cells to replace the thymocytes damaged during thymus regeneration

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is a major costimulatory receptor that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. The interaction of 4-1BB with 4-1BBL regulates immunity and promotes the survival and expansion of activated T cells. In this study, the expression of 4-1BB and 4-1BBL was examined during regeneration of the murine thymus following acute cyclophosphamide-induced involution. Four-color flow cytometry showed that 4-1BB and 4-1BBL were present in the normal thymus and were preferentially expressed in the regenerating thymus, mainly in CD4+CD8+ double-positive (DP) thymocytes. Furthermore, the CD4loCD8lo, CD4+CD8lo and CD4loCD8+ thymocyte subsets, representing stages of thymocyte differentiation intermediate between DP and single-positive (SP) thymocytes, also expressed 4-1BB and 4-1BBL during thymus regeneration but to a lesser degree. Interestingly, the 4-1BB and 4-1BBL positive cells among the CD4+CD8+ DP thymocytes present during thymus regeneration were TCR(hi) and CD69+ unlike the corresponding controls. Moreover, the 4-1BB and 4-1BBL positive cells among the intermediate subsets present during thymus regeneration also exhibited TCRhi/int and CD69+/int phenotypes, indicating that 4-1BB and 4-1BBL are predominantly expressed by the positively selected population of the CD4+CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

Abstract In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-kappaB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.

Effects of Indomethacin on Ischemia-induced Brain Injury / 대한해부학회지

Cerebral ischemia can have severe results and disrupt quality of life. Current medicine is not effective at overcoming these problems. To find out more effective therapies, it is necessary to understand the microenvironment of cerebral injury after the ischemia. In the present study, to investigate the effects of inflammatory reaction, indomethacin, an anti-inflammatory drug, was used in a photothrombotic focal infarction rat model. It was revealed that cerebral ischemia increased neurogenesis in the subventricular (SVZ) and subgranular zones (SGZ), and in the penumbral region. Indomethacin treatment reduced the cerebral ischemia-induced neurogenesis by 86.2%, 53.8%, and 52.8% respectively. Cerebral ischemia increased gliosis and angiogenesis in the penumbral region and indomethacin reduced gliosis and angiogenesis by 48.2% and 58.1%, respectively. These results suggest that indomethacin treatment after the cerebral ischemia can reduce neurogenesis, angiogenesis, and gliosis in the penumbral region.

Effects of retinoic acid on ischemic brain injury-induced eurogenesis

Neurogenesis can be induced by pathological conditions such as cerebral ischemia. However the molecular mechanisms or modulating reagents of the reactive neurogenesis after the cerebral ischemia are poorly characterized. Retinoic acid (RA) has been shown to increase neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain neuroblasts. Here, we examined whether RA can modulate the reactive neurogenesis after the cerebral ischemia. In contrast to our expectation, RA treatment decreased the reactive neurogenesis in subventricular zone (SVZ), subgranular zone (SGZ) and penumbral region. Furthermore, RA treatment also decreased the angiogenesis and gliosis in penumbral region.

Expression of CD70 during Thymus Regeneration in the Rat / 대한해부학회지

The thymus is the central lymphoid organ for development of bone marrow-derived precursor cells into mature T-cells. The thymic stroma provides the specialized microenvironment for the proliferation, differentiation, and maturation of the immature T-cells, thymocytes. The CD27 is a tumor necrosis factor (TNF) receptor family member whose expression is limited to cells of the lymphoid lineage. CD70, the ligand of CD27, is a TNF related trans-membrane protein induced upon activation on T and B cells, dendritic cells and macrophages. CD70/CD27 interaction plays a key role in T dependent B cell responses and is responsible for plasma cell differentiation. This study was performed to investigate the expression of CD70 during regeneration following acute involution induced by cyclophosphamide (CY) in the rat thymus using RT-PCR analysis and single and double immunohistochemistry. The results from RT-PCR analysis showed that CD70 is expressed in mouse thymic medullary interdigitating (IDC)-like cells (MDC), DC2.4 and Raw264.7 but not expressed in the mouse thymic epithelial cells (subcapsular/cortex epithelial cells, cortical epithelial cells and medullary epithelial cells). Interestingly, upregulation of CD70 expression was observed in the thymic stromal cells and thymocytes isolated from rat thymus during thymus regeneration. Furthermore, immunohistochemistry demonstrated that CD70 was mainly expressed in the ED1 positive macrophages predominantly in the thymic cortex both in the normal thymus and during thymus regeneration. In line with the data obtained by biochemical analysis, CD70 immunoreactive macrophages is increased both in number and in size during thymus regeneration. Thus, the results of the present study suggest that CD70 expressed on the thymic macrophages could play a role in the development of new T cells to replace T cells damaged by cyclophosphamide treatment during thymus regeneration.

Morphological Changes of Anterior Horn Cells of Lumbar Spinal Cord after Anterior Root Avulsion in Adult Rat / 대한해부학회지

The morphological changes in the anterior horn of the L4 and L5 spinal segments were observed following anterior root avulsion in the adult male Sprague-Dawley rat (300~350 gm) at 5 days, 1 week, 2 weeks and 3 weeks postlesion. The animals were perfused with 4% paraformaldehyde, 0.15% picric acid in 0.1 M phosphate buffer solution and cryostat sections were prepared. Immunohistochemistry was used to identify changes of the phenotype in the anterior horn cells. Primary antibodies, goat anti-choline acetyltransferase (ChaT, 1 : 500, Chemicon), mouse antirat ED-1 (1 : 200, Serotec), rabbit anti-glial fibrillary acidic protein (GFAP, 1 : 200, DAKO) and rabbit anti-vascular endothelial growth factor (VEGF, 1 : 500, Santa Cruz Biotechnology) were used. Avidin-Biotin complex method was performed for immunohistochemical reaction and color reaction was developed with DAB-H2O2. Following results were observed in the anterior horn of lumbar spinal cord; 1. The number of ChaT-immunoreactive (ir) cells were reduced 20% level of control animals at 3 weeks after avulsion. 2. ED-1-ir microglia were significantly increased at 1 week and processes of ED-1-ir microglia surrounded around the axotomized neuronal cell bodies. 3. Gliosis defined by extensive GFAP immunoreactivity was observed both ipsilateral and contralateral side of lesion but the VEGF-ir cells were significantly increased in the ipsilateral side of lesion. Therefore, this study suggested that the majority of axotomized motor neurons were degenerated and the cellular proliferation and phenotype changes including glial cell activation were observed in the lumbar spinal cord after anterior root avulsion of adult rats.

DNA Microarray Analysis of Gene Expression Profiles in Aging process of Mouse Brain

In order to investigate the molecular basis of the aging process in brain, we have employed high-density oligonucleotide microarrays providing data on 10,108 gene clusters to define transcriptional patterns in three brain regions, cerebral cortex, cerebellum, and hippocampus. Comparison of the expression patterns between young (6-week-old) and aged (17-month-old) C57BL/6 male micerevealed that about ten percent (1098) of the genes showed a significant change in the expression level in at least one of the three tissues. Among them, 23 genes were upregulated and 62 genes were downregulated in all three tissues of the old mice. The number of genes upregulated exclusively in hippocampus (337) was much larger compared to other tissues. Gene ontology-based analysis showed the genes related with signal transduction or molecular transports are more likely to be upregulated than downregulated in the aging process of hippocampus. These data may provide some useful means for elucidating the molecular aspect of aging in hippocampus and other regions in brain.

Roles of Hedgehog Signaling in the Neurodevelopment / 대한해부학회지

No abstract available.

Patterning of Ventral Neural Tube in Tg737(oprk) Mutant / 대한해부학회지

Polaris, which is encoded by Tg737 gene, has been associated with cilia formation. Recently pheno-types of ventral neural tube in mice who have abnormal cilia formation have been reported to be similar with those of sonic hedgehog (Shh)signaling mutants. These interesting findings lead us to further examine the patterning of ventral neural tube in Tg737(oprk) mice. In this study, we found that motor neuron and V2 interneuron were preserved whereas P3 progenitor domain and floor plate were missing in Tg737(oprk) mutant. V2 and motor neurons in Tg737(oprk) were ventralized and ixed with each other. Nkx6.1 and Olig2 expressions were preserved and the Olig2 expression was ventralized in Tg737(oprk). These penotypes are quite similar with those in Shh(-/-); Gli3(-/-) or Gli2(-/-) ; Gli3(-/-) mutants, suggesting that the function of Polaris might be involved in Shh signaling.

Roles of Gli3 in Dorsal Neural Tube / 대한해부학회지

Essential roles of Gli3 in ventral neural tube have been stressed from studies of Shh(-/-) and Shh(-/-); Gli3(-/-) mutants. However, roles of Gli3 in dorsal neural tube have not been fully appreciated despite of its high expression. To find out roles of Gli3 in dorsal neural tube, we studied cell proliferation and neuronal differentiation in dorsal neural tube of Gli3(-/-) mutant. In Gli3(-/-) mutant, proliferation of progenitor cells in dorsal neural tube is increased compared to wild type embryos based on phosphohistone 3 immunohistochemistry and BrdU experiment. The appearances of HuC/D positive and Isl1 postive cells which represent postmitotic neurons and dI3 interneurons were delayed in Gli3(-/-) mutant compared to wild type embryo. The appearance of a proneural gene, Ngn2 was also delayed in Gli3(-/-) mutant compared to wild type embryo. Neuronal differentiation of progenitor cells in dorsal neural tube was delayed in Gli3(-/-) mutant compared to wild type embryos based on HuC/D, Isl1 and Ngn2 expressions. These results suggest that Gli3 plays important roles in cell proliferation and neuronal differentiation in dorsal neural tube. Thus our data shed a new light on the role of Gli3 in the development of neural tube.

Roles of Gli3 in the Establishment of Progenitor Domains of Developing Spinal Cord / 대한해부학회지

University Sonic hedgehog (Shh) signaling has been shown to play instructive roles in developing spinal cord. Depending on the Shh concentration gradient, different progenitor domains and ventral neurons are induced. However, the way how the Shh gradient is translated into different progenitor domains, is not clear. To investigate the translation of the Shh gradient, we studied expressions of homeoproteins which are critical for establishment of progenitor domains, in the ventral neural tube of Shh(-/-)and Shh(-/-);Gli3(-/-) mutants, using in situ hybridization. In Shh(-/-) mutant, the expressions of class II homeoproteins (Nkx6.1, Nkx6.2, Olig2, Nkx2.2 were totally repressed. The expressions of class I homeoproteins (Dbx1, Dbx2, Irx3, Pax6 were ventralized. In Shh(-/-);Gli3(-/-) mutant, the expressions of class II homeoproteins except Nkx2.2 were restored. The expressions of class I home-oproteins were restored to its original position although their restoration is not complete. From above results, we conclude that Gli3 can regulate the expressions of class II homeoproteins, which suggests that the Shh gradient will be translated into Gli activity in the developing spinal cord.

Expressions of BMP Antagonists in Shh -/- ; Gli3 -/- Mutant / 체질인류학회지

Sonic hedgehog (Shh) has been known as an essential morphogen for the generation of motor neuron in developing spinal cord. However, motor neuron can be generated in Shh -/- ; Gli3 -/- or Gli2 -/- ; Gli3 -/- mutants although these mutants don't have Shh signaling. To find out the compensatory mechanism for the generation of motor neuron in Shh -/- ; Gli3 -/- mutant, we studied bone morphogenetic protein (BMP) antagonists including follistatin, flik and noggin, and retinoic acid signaling in this mutant. To study expressions of BMP antagonists, we performed in situ hybridization. To examine an activity of retinoic acid, we measured beta -galactosidase activity in retinoic acid response element (RARE) transgenic mouse. The expression of follistatin was reduced at both levels of forelimb and hindlimb in Shh -/- mutant compared to wild type embryo. It was restored at the level of forelimb but reduced at the level of hindlimb in Shh -/- ; Gli3 -/- mutant compared to wild type. The expression of flik was similar with wild type embryo at both levels of forelimb and hindlimb in Shh -/- mutant. The expression of flik was similar with wild type embryo at the level of forelimb however reduced in hindlimb level in Shh -/- ; Gli3 -/- mutant. The expression of noggin, a BMP antagonist, was increased in Shh -/- mutant. Activity of retinoic acid signaling was not affected in Shh -/- or Shh -/- ; Gli3 -/- mutants. From these results, we conclude that retinoic acid but not follistatin and flik, may be involved in the generation of motor neuron in Shh -/- ; Gli3 -/- mutant.

Expression of the ED3 Antigen and its Upregulation after Cyclophosphamide Treatment on Basal Epithelial Cells of Rat Stratified Squamous Epithelium / 대한해부학회지

Sialoadhesin (Sn) expression has been demonstrated on murine and rat macrophages in lymphatic organs and is recognized by the monoclonal antibody (mAb) ED3 in the rat. Sialoadhesin (Siglec-1), the ED3 antigen in the rat, is a subtype of sialic acid -binding Ig-like lectins (Siglecs) that bind specifically to sialic acid-containing structures such as selectins and was originally identified as the sheep erythrocyte receptor (SER) responsible for sialic acid-dependent binding of native sheep erythrocytes (SE) to resident murine bone marrow macrophages in rosetting assays. The aim of the present study was to investigate the expression and potential function of sialoadhesin in the stratified squamous epithelium of the rat tongue, esophagus and skin. The expression of sialoadhesin was demonstrated by immunohistochemical analysis with the mAb ED3. This study demonstrated not only the presence of sialoadhesin on the basal epithelial cells of the stratified epithelium in normal rat tongue, esophagus and skin but also its upregulated expression on these cells in CY-treated rats. The results of the present study shed some light on the potential function of sialoadhesin in the basal epithelial cells of the stratified epithelium. Further studies may provide more insight into the role of sialoadhesin in the epithelial stem cells.

Ultrastructure of Different Types of Thymic Epithelial Cells in the Rat Thymus / 대한해부학회지

Thymic epithelial cells constitute a major component of the thymic microenvironment. The thymus is involved in the regulation of the proliferation, maturation and differentiation of thymocytes. There is some controversy about the classification of thymic epithelial cell types. Traditionally, thymic epithelial cells have been divided into cortical and medullary epithelial cell types. In general, the thymic epithelium can be broadly subdivided into subcapsular, cortical and medullary epithelial cells, and Hassall's corpuscles by immunocytochemical methods. Although a few studies were performed on the ultrastructural characteristics of the different types of thymic epithelial cells, there is still some controversy about the classification of thymic epithelial cell subsets. Thus, the present study was performed to investigate the ultrastructural features of thymic epithelial cell subsets in adult male Sprague-Dawley rats, which are the most commonly used species of rat for biological researches, using transmission electron microscopy to shed more light on the heterogeneity of thymic epithelial cells. On the basis of ultrastructural features, we could identify and classify eight subsets of epithelial cells in normal rat thymus. In particular, this study provided a clear and easy way to identify the type 3 epithelial cells by their characteristic 'perinuclear arrangement pattern of relatively short bundles of tonofilaments'. This is an important finding since the type 3 epithelial cells has been considered to be the most difficult type to identify among various thymic epithelial cell types. The results of the present ultrastructural study of thymic epithelial cells provided more insight into the heterogeneity of thymic epithelial cells, and can contribute to the understanding of roles played by different types of thymic epithelial cells.

Gene Therapy with Adenoviral GDNF Vector in the Animal Model of Parkinson's Disease / 대한해부학회지

A recombinant adenoviral vector encoding human GDNF gene (Ad -GDNF) was developed to investigate the effect of GDNF gene in 6 -OHDA -induced Parkinson's disease rat. The changes of rotatory behavior and density of TH -immunoreactive axon terminals and number of cell bodies were observed by the GDNF expression. Adult male Sprague -Dawley rats were used. Parkinson's disease (PD) rat models were prepared by the injection of 6 -OHDA into the striatum. After 1 week, the animals showing apomorphine -induced rotatory behavior above 7 turns/ min were defined as PD rat model. Ad -GDNF was injected into the striatum of animal model and tested the apomorphine -induced rotatory behavior at 1 week after injection. These animals were perfused with Zamboni fixative to investigate the morphological changes after rotatory behavior test. Instead of Ad -GDNF, Ad -LacZ injected PD rats were used as a control. The following results are obtained: 1. The apomorphine -induced rotational behavior was significantly reduced by the treatment of PD rat by the injection of Ad -GDNF. The Ad -LacZ injected PD rat showed no change in rotatory behavior. 2. The density of TH -ir axon terminals in the striatum was significantly increased by the Ad -GDNF injection (75% of normal side), but there was no change in the density by the Ad -LacZ injection (37% of normal side) compared to 6 - OHDA lesioned striatum. This means the Ad -GDNF injection prevented the degenerative change of TH -ir axon terminals in the stritum of the PD rat. 3. The number of TH -ir cell body was significantly recovered by the Ad -GDNF (82% of normal side), but there was not recovered by the Ad -LacZ injection (60% of normal side) compared to 6 -OHDA lesion. This means the retrogradely transported Ad -GDNF induced the TH expression in the dopaminergic neurons of the substantia nigra. Gene therapy with Ad -GDNF prevented the degeneration of dopaminergic neurons and axon terminals in the 6 - OHDA -induced PD rat.

Phosphorylation of 46-kappa Da protein of synaptic vesicle membranes is stimulated by GTP and Ca2+/calmodulin

The release of neurotransmitter is regulated in the processes of membrane docking and membrane fusion between synaptic vesicles and presynaptic plasma membranes. Synaptic vesicles contain a diverse set of proteins that participate in these processes. Small GTP-binding proteins exist in the synaptic vesicles and are suggested to play roles for the regulation of neurotransmitter release. We have examined a possible role of GTP-binding proteins in the regulation of protein phosphorylation in the synaptic vesicles. GTPgammaS stimulated the phosphorylation of 46 kappa Da protein (p46) with pI value of 5.0-5.2, but GDPbetaS did not. The p46 was identified as protein interacting with C-kinase 1 (PICK-1) by MALDI-TOF mass spectroscopy analysis, and anti-PICK-1 antibody recognized the p46 spot on 2-dimensional gel electrophoresis. Rab guanine nucleotide dissociation inhibitor (RabGDI), which dissociates Rab proteins from SVs, did not affect phosphorylation of p46. Ca2+/ calmodulin (CaM), which causes the small GTP- binding proteins like Rab3A and RalA to dissociate from the membranes and stimulates CaM- dependnet protein kinase(s) and phosphatase, strongly stimulate the phosphorylation of p46 in the presence of cyclosporin A and cyclophylin. However, RhoGDI, which dissociates Rho proteins from membranes, reduced the phosphorylation of p46 to the extent of about 50%. These results support that p46 was PICK-1, and its phosphorylation was stimulated by GTP and Ca2+/CaM directly or indirectly through GTP-binding protein(s) and Ca2+/CaM effector protein(s). The phosphorylation of p46 (PICK-1) by GTP and Ca2+/CaM may be important for the regulation of transporters and neurosecretion.