Biomedical subjects

Chong Jai Kim

Publications and source records attributed to Chong Jai Kim.

At least 19 recordsLinked to original sources

PubMed2006

Genetic origin and proportion of basal plate surface-lining cells in normal and abnormal pregnancies.

The human placenta is a transient organ, the villous surface of which is in direct contact with the maternal circulation during pregnancy. Thus, the syncytiotrophoblast and the basal plate-lining cells are considered continuous with the endothelial layer of the maternal vasculature. Two types of cells are found on the surface of the basal plate: trophoblasts (of fetal origin) and endothelial cells of putative maternal origin. Histologic abnormalities have been described in the basal plate of the placenta obtained from patients with preeclampsia and intrauterine growth restriction. Moreover, endothelial cell dysfunction and intravascular inflammation are key features of preeclampsia. The objectives of this study were to: (1) determine the origin of the endothelial cells located in the basal plate surface of the placenta (from male fetuses); and (2) analyze the relative proportion of the intervillous surface of the basal plate occupied by trophoblasts and endothelial cells. Immunohistochemistry and morphometry were performed in placentas from women in the following clinical groups: (1) normal-term pregnancies (n = 15); (2) severe preeclampsia at term (n = 15); (3) small-for-gestational-age (SGA) neonates delivered at term (n = 15); (4) preterm deliveries (<37 weeks) without inflammation (n = 5); and (5) preterm preeclampsia (n = 5). Laser capture microdissection and polymerase chain reaction were used to determine the allelic pattern of the amelogenin gene of the endothelial cells on the intervillous surface of the basal plate. Our results showed that: (1) the endothelial cells lining the basal plate in placentas of male fetuses were uniformly of maternal origin; and (2) in placentas from uncomplicated pregnancies, the median proportion of trophoblasts and endothelial cells covering the surface of the basal plate were 27.7% and 46.5%, respectively. The remaining area of the intervillous surface of the basal plate was composed of fibrin and anchoring villi. Of interest, placentas from women who delivered an SGA neonate had a higher proportion of trophoblasts and a lower proportion of endothelial cells lining the basal plate than those from normal pregnancies (P < .05). The same tendency was observed in placentas from patients with preeclampsia. This study demonstrates that endothelial cells of maternal origin cover the intervillous surface of the basal plate of the placenta, along with trophoblasts of fetal origin. The proportion of this surface lined by trophoblasts is greater in placentas from SGA and preeclampsia than in normal pregnancy. We propose that this change reflects a compensatory mechanism whereby the basal plate surface covered by injured endothelial cells is replaced by trophoblasts or results from a failure of trophoblastic involution in abnormal pregnancies. Our observations also suggest that the lining of the basal plate can provide information about the pathology of endothelial cells in complications of pregnancy.

Adolescent↗

PubMed2006

Arsenic trioxide concentration determines the fate of Ewing's sarcoma family tumors and neuroblastoma cells in vitro.

Arsenic trioxide (As(2)O(3)) induces both the differentiation and apoptosis of acute promyelocytic leukemia cells in a concentration dependent manner. We assessed the effects of As(2)O(3) in CADO-ES Ewing's sarcoma (ES), JK-GMS peripheral primitive neuroectodermal tumor (PNET), and SH-SY5Y neuroblastoma cells, as they share common histogenetic backgrounds. As(2)O(3) at low concentrations (0.1-1 microM) induced SH-SY5Y differentiation, and whereas PNET cells acquired a slightly differentiated phenotype, change was minimal in ES cells. Extracellular signal-regulated kinase 2 (ERK2) was activated at low As(2)O(3) concentrations, and PD98059, an inhibitor of MEK-1, blocked SH-SY5Y cell differentiation by As(2)O(3). High concentrations (2-10 microM) of As(2)O(3) induced the apoptosis in all three cell lines, and this was accompanied by the activation of c-jun N-terminal kinase. The generation of H(2)O(2) and activation of caspase 3 were identified as critical components of As(2)O(3)-induced apoptosis in all of the above cell lines. Fibroblast growth factor 2 enhanced As(2)O(3)-induced apoptosis in JK-GMS cells. The overall effects of As(2)O(3) strongly suggest that it has therapeutic potential for the treatment of ES/PNET.

Antineoplastic Agents↗

PubMed2006

Relationship between maternal and fetal plasma glucose and insulin concentrations during graded maternal hyperglycemic states in primates.

Our goal was to conduct a controlled study using an established timed-pregnant baboon model to describe the maternal and fetal plasma glucose and insulin concentrations during graded increases in maternal circulating glucose levels. Timed-pregnant baboons were operated on during the second half of pregnancy, and after recovery from surgery, maternal glucose infusions were started. To determine changes in plasma glucose and insulin concentrations, maternal and fetal blood samples were obtained before glucose infusion and at 30-minute intervals to include 30 minutes postinfusion. Maternal plasma glucose concentrations ranged from 97 to 392 mg/dL and fetal plasma glucose concentrations from 78 to 278 mg/dL. Maternal plasma insulin concentrations ranged from 123 to 1384 U/mL, and the fetal plasma insulin concentrations from 76 to 260 U/mL. Significant correlations were noted between maternal plasma glucose and insulin concentrations (N = 10; R(2), 80%; P < 0.001), as well as maternal and fetal plasma glucose concentrations (N = 10; R(2), 97%; P < 0.001). Maternal-to-fetal glucose gradient ranged from 16 to 34% (mean, 23%) and did not correlate with maternal plasma glucose concentration. No correlation was found between fetal plasma glucose and insulin concentration. Maternal-to-fetal insulin gradient ranged from 31 to 87% (mean, 70.7%) and was significantly different from the glucose gradient ( P < 0.0001). Results from this study suggests that (1) there is a relatively steady transplacental glucose transfer during the second half of pregnancy at maternal plasma glucose concentrations ranging from 97 to 392 mg/dL; and (2) there is also a relative incapacity of the fetal pancreas, compared with the maternal pancreas, to respond to graded increases of hyperglycemia. Studies aimed at determining whether particular thresholds of maternal hyperglycemia at different gestational ages can lead to transitory hyperosmolar and polyuric fetal states could provide further insights into the mechanisms leading to idiopathic polyhydramnios.

Animals↗

PubMed2006

Proteome analysis of human amnion and amniotic fluid by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Proteome analysis by 2-DE and PMF by MALDI-TOF MS was performed on human amnion and amniotic fluid at term. Ninety-two soluble and nineteen membrane proteins were identified from amnion. Thirty-five proteins were identified from amniotic fluid. Calgranulin A and B were found in all patients infected with Ureaplasma urealyticum, but not in any of the patients without infection, indicating that they are potential markers of intrauterine infection. Identity of calgranulin A and B was confirmed by MALDI-TOF/TOF MS. This study represents the first extensive analysis of the human amnion and amniotic fluid proteome at term and demonstrates that 2-DE and MALDI-TOF MS is a useful tool for identifying clinically significant biomarkers of problematic pregnancies.

Amino Acid Sequence↗

PubMed2006

Fetal macrophages are not present in the myometrium of women with labor at term.

OBJECTIVE: The basic mechanisms responsible for human parturition remain to be elucidated. The influx of fetal leukocytes into the myometrium has been recently proposed to be a crucial event in the onset of murine parturition. Surfactant protein-A has been implicated in the initiation of labor. In mice, it is thought that surfactant protein-A induces migration and subsequent activation of amniotic fluid macrophages of fetal origin, which then invades the myometrium. The present study was conducted to determine whether fetal macrophages invade the myometrium of women in labor. STUDY DESIGN: Placental bed biopsy specimens were obtained from patients in labor who delivered male neonates at term (n = 7). Myometrial sections of postpartum hysterectomy specimens obtained from women who delivered of male neonates (n = 3) were also analyzed. Formalin-fixed, paraffin-embedded sections were immunostained for CD68 or CD14 (which are markers for macrophages); immunoreactive myometrial macrophages were specifically procured by laser capture microdissection. Sex typing was done by polymerase chain reaction for the amelogenin gene with genomic DNA that was isolated from the macrophages. Chromogenic in situ hybridization with a Y chromosome-specific probe was also performed on paraffin-embedded histologic sections. RESULTS: Amelogenin allelotypes of the macrophages were consistent with female alleles in all cases that were tested, indicating a maternal origin. Chromogenic in situ hybridization demonstrated the absence of Y chromosome-positive mononuclear cells in the myometrium in all cases. CONCLUSION: These observations, from a limited number of cases, suggest that migration of fetal macrophages from the amniotic cavity or the chorioamniotic membranes into the myometrium does not occur during human labor. The trafficking of fetal macrophages in labor seems to be different in humans and mice.

Female↗

PubMed2006

Tissue microarray: an effective high-throughput method to study the placenta for clinical and research purposes.

OBJECTIVE: Tissue microarray (TMA) technology allows simultaneous examination of the expression of many molecular markers (protein, mRNA, DNA, etc.) with high-throughput. The application of this technology, to date, has been largely confined to the study of cancer. Placental pathology poses unique challenges because of the size of the organ, its complex anatomy, as well as its histological heterogeneity. The objective of this study was to assess the feasibility and efficiency of TMAs for immunohistochemistry and in situ hybridization of placental tissues. STUDY DESIGN: TMAs were constructed using an automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used. Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in each block. Five mum-thick TMA sections underwent immunohistochemical analysis of both cytoplasmic and nuclear antigens using a panel of antibodies against a variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF), and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens. mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in situ hybridization for the Y chromosome (DYZ1) were also performed. RESULTS: Validation of TMA immunoreactivity demonstrated comparable results with corresponding whole sections. When a two-tiered scoring system (positive/negative) was employed, there was agreement between two and three cores and whole tissue sections (kappa>0.7). When a three-tiered scoring system (negative, weak-positive, or strong-positive) was used, the data from three cores showed the highest agreement with whole tissue sections (kappa >0.7). In situ hybridization experiments for mRNA and DNA were also successful in that the signals were readily detectable. Successful transfer from the donor block to the recipient block differed according to the anatomical compartment. The transfer efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were 96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. CONCLUSION: TMA is a practical and effective tool for high-throughput molecular analysis of the human placenta. Duplicate and triplicate cores offer agreement with whole tissue sections for two-category distinction immunostaining. TMA also affords relevant results from in situ hybridization experiments for mRNA and DNA. The major advantages are the conservation of tissues and reagents, simultaneous comparison of molecular markers in different anatomical compartments of the placenta, and reduction of experimental error.

Biomarkers↗

PubMed2006

A role of the anti-angiogenic factor sVEGFR-1 in the 'mirror syndrome' (Ballantyne's syndrome).

BACKGROUND: 'Mirror syndrome' (Ballantyne's syndrome) refers to the association of fetal hydrops with placentomegaly and severe maternal edema. Preeclampsia occurs in approximately 50% of these cases. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), an anti-angiogenic factor, has been implicated in the pathophysiology of preeclampsia (PE). OBJECTIVE: The objective of this study was to determine if the maternal plasma concentration of sVEGFR-1 is elevated in patients with mirror syndrome. STUDY DESIGN: This case-control study included patients with uncomplicated pregnancies (n = 40) and those with mirror syndrome (n = 4) matched for gestational age. Mirror syndrome was defined as fetal hydrops and severe maternal edema. Maternal plasma sVEGFR-1 concentrations were determined using specific enzyme-linked immunosorbent assays. Immunohistochemistry of sVEGFR-1 on villous trophoblasts was also performed in samples from one patient with mirror syndrome and compared with those from a patient with spontaneous preterm delivery matched for gestational age. Non-parametric statistics were used for analysis (p < 0.05). RESULTS: (1) The median maternal plasma concentration of sVEGFR-1 was significantly higher in patients with mirror syndrome than in the control group (median: 3974 pg/mL, range: 3083-10 780 vs. median: 824 pg/mL, range: 260-4712, respectively; p < 0.001). (2) All patients with mirror syndrome had sVEGFR-1 concentrations above the 95th percentile for gestational age. Syncytiotrophoblast, especially syncytial knots, showed strong staining with antibodies against sVEGFR-1 in placental samples from the patient with mirror syndrome, but not in those from the patient with spontaneous preterm delivery. CONCLUSION: High maternal plasma concentrations of sVEGFR-1 were observed in mirror syndrome. We propose that this anti-angiogenic factor may participate in the pathophysiology of this syndrome. Thus, maternal plasma determination of sVEGFR-1 may help to identify the hydropic fetus that places the mother at risk for preeclampsia.

Adult↗

PubMed2006

Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation.

OBJECTIVE: Funisitis is the histologic counterpart of the fetal inflammatory response syndrome, which is a multisystemic disorder associated with impending preterm delivery and adverse neonatal outcome. The purpose of this study was to examine the relationship between funisitis and the microbiologic status of amniotic fluid (AF) and AF white blood cell (WBC) count in patients at term. METHODS: The relationship between the presence of funisitis, AF culture, and AF WBC count was examined in 832 consecutive patients who delivered a term neonate within 72 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly. AF WBC count was analyzed in a hemocytometer chamber. Nonparametric statistics were used for data analysis. RESULTS: Funisitis was present in 4% (30/832) of cases. A positive AF culture was more common in cases with funisitis than in those without funisitis (17% vs. 5%; p < 0.05). Patients with funisitis had a significantly higher median AF WBC count than those without funisitis (median >1000 cells/mm3 vs. median 2 cells/mm3; p < 0.001). The frequency of funisitis and of a positive AF culture was 1% in women without labor and with intact membranes and the frequencies and the median AF WBC count increased in the presence of labor or rupture of membranes. CONCLUSION: Funisitis is present in 4% of women at term and is associated with microbial invasion of the amniotic cavity (MIAC) and inflammation as reflected by increased AF WBC count.

Adult↗

PubMed2006

Normal and abnormal transformation of the spiral arteries during pregnancy.

This article reviews the anatomy and physiology of the uterine circulation, with emphasis on the remodeling of spiral arteries during normal pregnancy, and the timing and anatomical pathways of trophoblast invasion of the spiral arteries. We review the definitions of the placental bed and basal plate of the placenta, their relevance to the study of the physiologic transformation of the spiral arteries, as well as the methods to obtain and examine placental bed biopsy specimens. We also examine the role of the extravillous trophoblast in normal and abnormal pregnancies, and the criteria used to diagnose failure of physiologic transformation of the spiral arteries. Finally, we comment on the use of uterine artery Doppler velocimetry as a surrogate marker of chronic uteroplacental ischemia.

Arteries↗

PubMed2005

Differential activation of mitogen activated protein kinases and nuclear factor-kappaB in lipopolysaccharide-treated term and preterm amnion cells.

Intrauterine exposure to amniotic sac infection elicits an inflammatory response from the fetus, which is associated with elevated levels of fetal plasma proinflammatory cytokines, i.e. interleukin-6 (IL-6). We have recently demonstrated that the severity of fetal inflammatory response in terms of gestation period is greater in preterm fetuses than in term fetuses. The activation of mitogen activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) is known to be associated with up-regulation of proinflammatory cytokine gene expression in many cell types. In the present study, therefore, we studied patterns of MAPK and NF-kappaB activation following treatment with bacterial lipopolysaccharide (LPS) in amnion cells obtained from placentas of varying gestational ages to assess whether or not MAPKs and NF-kappaB are differentially regulated during gestation. MAPK phosphorylation was investigated by immunoblot analysis with phosphospecific antibodies. Transient phosphorylations of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) were observed in LPS-treated amnion cells, with the degree of phosphorylation being more pronounced in preterm cases. The results of NF-kappaB-dependent reporter gene expression and electrophoretic mobility shift assay (EMSA) of NF-kappaB were similar to those of ERK 1/2 and JNK activity. To assess whether the results of in vitro observations reflected in vivo results, we further analyzed amniotic fluid and cord blood IL-6 levels in preterm deliveries with placental inflammation. The analysis also revealed a significantly higher level of IL-6 in cases of </=31 weeks gestation when compared with those of more than 31 weeks (P<0.001). All these findings strongly suggest that there is an inverse relationship between gestational age and fetal inflammatory response during human gestation, and that differences in the intensity of MAPK activation and NF-kappaB-dependent transcription pathways are elements of the major underlying mechanism.

Adult↗

PubMed2005

HUlip, a human homologue of unc-33-like phosphoprotein of Caenorhabditis elegans; Immunohistochemical localization in the developing human brain and patterns of expression in nervous system tumors.

HUlip is a human homologue of a C. elegans gene, unc-33, that is developmentally regulated during maturation of the nervous system. HUlip is highly expressed only in the fetal brain and spinal cord, and is undetected in the adult brain. The purpose of this study was to investigate the pattern of hUlip expression in the developing human brain and nervous system tumors. Ten human brains at different developmental stages and 118 cases of nervous system tumor tissues were examined by immunohistochemistry. Twelve related tumor cell lines were also analyzed by northern blotting and immunoblotting. HUlip was expressed in late fetal and early postnatal brains; strongly in the neurons of the brain stem, basal ganglia/thalamus, and dentate gyrus of the hippocampus, and relatively weakly in the cerebral and cerebellar cortex. Among tumors, hUlip expression was easily detected in tumor cells undergoing neuronal differentiation such as ganglioneuroblastomas and ganglioneuromas. Furthermore, hUlip immunoreactivity was also found in various brain tumors showing neuronal differentiation: central neurocytomas (6 of 6 cases were positive), medulloblastomas (5/11), atypical teratoid rhabdoid tumor (1/1) and gangliogliomas (4/7). Some astrocytic tumors also showed weak positivity: astrocytomas (1 of 5 cases), anaplastic astrocytomas (2/5), and glioblastomas (3/11). Subependymal giant cell astrocytomas and subependymomas, which are of controversial histogenetic origin, showed strong hUlip immunoreactivity. The results of this study indicate that the expression of hUlip protein is distinctly restricted to the late fetal and early postnatal periods of human nervous system development and to certain subsets of nervous system tumors. The exact function of hUlip needs to be further clarified; yet the results of our study strongly imply that hUlip function is important in human nervous system development and its aberrant expression in various types of nervous system tumors suggests a role of hUlip as an oncofetal neural antigen.

Astrocytes↗

PubMed2005

Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition.

OBJECTIVE: The role of progesterone in the control of human parturition remains unsettled. Because there is no systemic progesterone withdrawal before the onset of labor, a 'functional progesterone withdrawal' has been proposed to be operative before human parturition. This may be accomplished by a change in the density of the progesterone receptor (PR) isoforms in myometrium and fetal membranes. The purpose of our study was to determine if spontaneous term labor is associated with changes of PR isoforms (PR-A and PR-B) in the fetal membranes. STUDY DESIGN: Fetal membranes were obtained from women undergoing elective cesarean delivery at term (not in labor group), and from women with a vaginal delivery (labor group). The expression of PR isoforms was assessed by Western blot analysis of amnion and chorio-decidua. Densitometric analysis of PR-A/PR-B ratio was performed. Immunohistochemistry with specific antibodies to PR-A and PR-B was done. Nonparametric statistics were used for analysis. RESULTS: 1) The predominant isoform of PR in women not in labor was PR-B, and PR-A in patients in labor. The ratio of PR-A/PR-B in fetal membranes was significantly higher in women in labor than in those not in labor (for amnion, median 4.3, range [0.9-8.4] vs median 0.4, range [0.3-2.6], P < .001; for chorio-decidua, median 2.0, range [1.1-19.2] vs median 1.2, range [0.1-2.0], P < .05). 2) Fetal membranes expressed both types of PR. 3) Immunohistochemistry showed the presence of PR-A and PR-B in the cytoplasm of amnion epithelial cells, chorion trophoblast, and decidual cells. CONCLUSION: Human parturition at term is associated with changes in PR isoforms in the fetal membranes and, thus, a local 'functional progesterone withdrawal' may operate in human parturition through this mechanism.

Blotting, Western↗

PubMed2005

Expression of bone morphogenetic protein 2 in normal spontaneous labor at term, preterm labor, and preterm premature rupture of membranes.

OBJECTIVE: Genome-wide screening studies of the chorioamniotic membranes unexpectedly identified an increase in the expression of bone morphogenetic protein 2 in spontaneous labor at term. The objective of this study was to determine whether bone morphogenetic protein 2 messenger RNA and protein expression are altered in the chorioamniotic membranes of patients with term labor, preterm labor, and preterm premature rupture of membranes. STUDY DESIGN: Chorioamniotic membranes were obtained from patients at term (with and without labor), with preterm labor (with and without histologic chorioamnionitis), and with preterm premature rupture of membranes (with and without histologic chorioamnionitis). The expression of bone morphogenetic protein 2 was studied by real-time quantitative reverse transcriptase-polymerase chain reaction (n = 88) and immunohistochemistry (n = 124). Nonparametric statistics were used for analysis. Primary amnion cells obtained from women at term not in labor were treated with bone morphogenetic protein 2 to examine whether there was increased prostaglandin E2 expression. RESULTS: The median bone morphogenetic protein 2 messenger RNA and protein expression were significantly higher in the membranes of patients with spontaneous labor at term than in those of patients not in labor at term (P < .001 for both). Bone morphogenetic protein 2 messenger RNA and protein expression were increased in patients with preterm labor with histologic chorioamnionitis than in those without histologic chorioamnionitis (P < .05 and P < .001, respectively). There was no difference in bone morphogenetic protein 2 messenger RNA and protein expression in patients with preterm premature rupture of membranes, regardless of chorioamnionitis (P = .13 and P = .08, respectively). There was a correlation between bone morphogenetic protein 2 and cyclooxygenase 2 protein expression in chorioamniotic membranes (R = .34; P < .001). CONCLUSION: Bone morphogenetic protein 2 messenger RNA and protein expression are increased in the chorioamniotic membranes of patients with spontaneous labor at term and patients with preterm labor associated with histologic chorioamnionitis. Its expression pattern and biologic effects strongly suggest that bone morphogenetic protein 2 is involved in human parturition.

Amnion↗

PubMed2005

Toll-like receptor 4: a potential link between "danger signals," the innate immune system, and preeclampsia?

OBJECTIVE: Toll-like receptors (TLRs) recognize microbial ligands and host products that are released during tissue damage, the so-called "danger signals." This study was conducted to determine whether changes in TLR-4 and TLR-2 expressions can be detected in the trophoblasts at the placental bed of women with and without preeclampsia. STUDY DESIGN: Placental bed biopsy specimens were obtained from women with: (1) normal term pregnancies with and without labor (each n = 20); (2) preeclampsia who delivered preterm (n = 15); and (3) preterm labor and intact membranes with and without chorioamnionitis (each n = 15). The expression pattern of TLR-4 and TLR-2 in the trophoblasts was analyzed by double immunohistochemistry. RESULTS: (1) The median percentage of TLR-4 positive interstitial trophoblasts was significantly higher in patients with preeclampsia than in patients with preterm labor without or with histologic chorioamnionitis (P = .0002 and P = .02, respectively). (2) The median percentage of TLR-2 positive interstitial trophoblasts was not different among the study groups (P>.05). (3) TLR-4 positive trophoblasts were also frequently immunoreactive to activated nuclear factor-kappaB, tumor necrosis factor-alpha, and M30 (a specific apoptosis antigen for trophoblast). (4) Lipopolysaccharide treatment inhibited the migration of trophoblast cell lines in vitro. CONCLUSION: TLR-4 protein expression is increased in interstitial trophoblasts of patients with preeclampsia. We propose that "danger signals" at the feto-maternal interface, which are recognized by trophoblasts through TLR-4, may play a key role in the creation of a local abnormal cytokine milieu. This suggests a novel mechanism that links the activation of the innate immune system through TLR-4 and preeclampsia.

Cell Movement↗

PubMed2005

Implantation of perichondrium-derived chondrocytes in physeal defects of rabbit tibiae.

BACKGROUND: Various cells and scaffolds have been used experimentally as interposition materials after physeal bar resection to treat partial physeal growth arrest. However, results of these cell therapies are unpredictable. METHODS: We investigated the chondrogenic differentiation of rabbit perichondrial cells in vitro. We also investigated radiographic and histological changes after implantation of the perichondrium-derived chondrocytes, embedded in fibrin beads, into defects created in the medial aspect of the proximal tibial physis of 26 8-week-old New Zealand White rabbits. Physeal defects of the contralateral tibiae were left intact without any treatment, or were treated with fibrin beads not containing cells. RESULTS: The perichondrial cells cultured in the alginate- fibrin beads were positive in immunohistochemical staining for S-100 protein and the extracellular area was stained with Safranin-O. RNase protection assay showed that the expression of type II collagen and aggrecan continued In the cell and bead-treated tibiae, varus deformity was reduced significantly and tibial length was maintained longer than that of the contralateral tibia. Histologically, cartilage clusters of varying size with intervening micro-bony trabeculae were found in the cell and bead-treated tibiae. The lateral, remaining physis in the untreated tibiae showed altered histology. INTERPRETATION: Implantation of fibrin beads containing perichondrium-derived chondrocytes into the physeal defect helps to prevent angular deformation and shortening of long bone, but not completely. Physeal bony bar formation adversely affects the growth of the remaining physis from early stages onward.

Animals↗

PubMed2005

Magnetic resonance imaging of remaining physis in partial physeal resection with graft interposition in a rabbit model: a comparison with physeal resection alone.

OBJECTIVE: The purpose of this study was to evaluate the effect of graft interposition into a physeal defect on the remaining physis. MATERIALS AND METHODS: Bilateral partial physeal defects were made in the medial half of the proximal tibiae of 8-week-old New Zealand white rabbits (n=25). Biologic material (autogenous chondrocytes derived from perichondrial cells incorporated into beads) was implanted in the left-sided physeal defect, and right-sided untreated tibial defects were used as controls. Magnetic resonance (MR) imaging was obtained at 2, 4, 8, 12, and 16 weeks after operation using a 1.5-tesla MR unit. T1WI, T2WI, and gradient-recalled echo (GRE) images were obtained in the coronal plane. The MR features of physeal defects and of remaining physes were compared between grafted tibiae and controls, as were histologic results and the heights of the remaining physes. RESULTS: Histologically, cartilage clusters were detected in the 17 cases of grafted tibiae (68%), whereas a bone bridge was observed in all controls. The cartilage clusters showed high signal intensity on both T2WI and GRE and low signal intensity on T1WI at 2 weeks postoperatively, and became low signal intensity on T2WI at 8 weeks. On GRE images, high signal intensities of the remaining physes disappeared earlier in the control tibiae than in the grafted tibiae. The remaining physes of control tibiae showed altered histologic configurations and a progressive decrease in physis height. Quantitative measurements of the height of the remaining growth plates showed a significant difference between grafted tibiae and controls (P <0.001). CONCLUSION: Graft interposition into a partial physeal defect may prevent early closure of the remaining physis and bone bridge formation. MR imaging can depict alterations of remaining physes that lead to early closure of the physis.

Animals↗

PubMed2005

Evaluation of testicular viability by power Doppler ultrasonography in experimentally induced acute testicular torsion.

RATIONALE AND OBJECTIVE: We sought to determine whether torsed testis viability can be evaluated by ultrasonography (US) including power Doppler US in an experimental model of acute testicular torsion. METHOD: Eighteen rats underwent unilateral 540 degrees testicular torsion and contralateral orchiopexy. Gray-scale and power Doppler US were performed 24 hours later. We evaluated echogenicity, intratesticular vascular flow, and testis size. Echogenicity and intratesticular vascular flow were quantitatively analyzed by using a visual scale and computer-based analysis. After US, detorsion was performed in torsed testes, and 6 days after detorsion testes were excised to determine testicular viability, which was determined using gross and microscopic findings. US findings before detorsion were correlated with testicular viability. RESULTS: At US performed 24 hours after testicular torsion, all viable testes (n = 7) were homogeneous and isoechoic versus contralateral testes. In nonviable testes (n = 11), lower (82%) and heterogeneous (73%) echogenicities were seen on gray-scale US. Intratesticular vascular flow was preserved in 86% of viable testes. In nonviable testes, no intratesticular vascularity was observed in 82%, and intermittent, peripheral blood flow was detected in the remaining 18%. Intratesticular focal lesions were observed in 45% of nonviable testis. Quantitative analysis showed a statistically significant difference between viable and nonviable testes in terms of testicular echogenicity and intratesticular vascular flow. CONCLUSION: Preoperative US including power Doppler examination can predict testicular viability in testicular torsion. Echogenicity of nonviable testes was found to be hypoechoic and inhomogeneous. Power Doppler examination showed no or intermittent peripheral blood flow in nonviable testes.

Acute Disease↗

PubMed2005

MR imaging findings of uveal leiomyoma: three cases.

Leiomyoma is a rare tumor arising from the uveal tract. Fundoscopically, it appears as a yellowish-white, elevated mass and cannot be readily distinguished from melanoma or other uveal tumors. Cross-sectional imaging may have an important role, particularly when the opaque ocular media or a vitreous hemorrhage precludes a clear ophthalmoscopic view. In this respect, radiologists should be aware of suggestive findings of uveal leiomyoma to avoid an incorrect diagnosis and unnecessary radical surgery. We report MR imaging findings of three cases of uveal leiomyoma.

Adult↗