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Biomedical subjects

J G Chi

Publications and source records attributed to J G Chi.

At least 19 recordsLinked to original sources

Cell kinetics of surgically induced spinal open neural tube defect in chick embryos.

In an attempt to understand cell kinetics of open neural tube defects (ONTDs) in the embryonic stages, chronological changes of cell proliferation and cell death patterns in the surgically induced spinal ONTDs of chick embryos were investigated using proliferating cell nuclear antigen (PCNA) staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) method. ONTDs were induced at Hamburger and Hamilton stages 17-19. Compared with the control group, the surgery group showed a lower PCNA labeling index for 5 days after surgery and demonstrated more TUNEL-positive cells at 6 h, 3 and 5 days after surgery. Decreased cell proliferation and enhanced apoptosis were seen in the ventral as well as in the dorsal spinal cord. These results partly explain the functional deficits of ONTDs.

Animals

Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas.

Cerebellar hemangioblastoma is a benign central nervous system neoplasm with characteristic proliferation of vascular and stromal cells. There is increasing evidence that the stromal cell population may represent the neoplastic component of hemangioblastoma, whereas the vascular component may be composed of reactive, nonneoplastic cells. Therefore, successful genetic testing for loss of heterozygosity requires selective analysis of target cell populations. Here, tissue microdissection was used to selectively analyze the stromal cell component of 20 archival sporadic cerebellar hemangioblastomas for loss of heterozygosity at the Von-Hippel Lindau (VHL) gene and somatic VHL gene mutations. Allelic deletions at the VHL gene locus were detected in the stromal cell component with one or more markers (D3S1038, D3S1110, and/or 104/105) in 10 of 19 (52.6%) informative cases. In all cases, heterozygosity at the VHL gene locus was retained in the vascular component. In two cases, aberrant bands in exon 2 of the VHL gene were demonstrated in the stromal cells by PCR-based single-strand conformation polymorphism analysis, and somatic missense mutations were successfully characterized in two of the sporadic hemangioblastomas by direct sequencing. The results suggest that allelic losses and mutations of the VHL tumor suppressor gene play a role in sporadic cerebellar hemangioblastoma tumorigenesis. Furthermore, because the genetic changes were detected in selectively procured stromal cell areas, the data provide strong evidence that the stromal cell represents a neoplastic component of hemangioblastoma.

Adolescent

Intramedullary anaplastic oligodendroglioma in a child.

Primary intramedullary anaplastic oligodendroglioma is a rare tumor, only four cases of which have been reported. The authors present the case of a 38-month-old boy with primary intramedullary anaplastic oligodendroglioma. He underwent partial removal of the tumor and spinal radiation therapy. The residual tumor disappeared 12 months after radiation, and 48 months after treatment there was no evidence of recurrence. This case shows that in primary intramedullary anaplastic oligodendroglioma, postoperative radiation therapy confined to the spinal cord can yield an optimal result.

Child, Preschool

Thymic epithelial tumor progression in an SV40T transgenic mouse model. Cortical thymoma-thymic carcinoma sequence.

There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We established a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma within a predictable time span. Using this animal model and a morphological approach, thymic epithelial tumour progression was studied with reference to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the entire spectrum from cortical type thymoma to thymic carcinoma. Thymic size tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiated thymic carcinoma. When SV40T TG mice (248 line) reached a certain age, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma-carcinoma sequence. When the mice were 9 weeks of age, the thymuses formed gross masses compatible with cortical thymoma. At 14 weeks of age, WDTC appeared against the background of cortical thymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullary thymomas did not develop in the mice, and no transition from medullary-type thymomas to thymic carcinomas was observed. In this SV40T transgenic mouse model, thymic carcinoma is clearly preceded by cortical-type thymoma. These transgenic mice may provide an interesting model for the progression from cortical thymoma to WDTC and/or high-grade carcinoma.

Aging

Hemophagocytic syndrome associated with occult B-cell lymphoma: an autopsy case.

Hemophagocytic syndrome has been observed in various disorders, including malignant histiocytosis, peripheral T-cell lymphoma, and viral or bacterial infections. However, B-cell lymphoma has seldom been associated with hemophagocytic syndrome. We report a case of B-cell lymphoma that was associated with hemophagocytic syndrome. The diagnosis was not made until the time of autopsy.

Aged

Short-rib polydactyly syndrome, Beemer-Langer type, with bilateral huge polycystic renal dysplasia: an autopsy case.

Short rib-polydactyly syndrome (SRPS) is a group of lethal skeletal dysplasia of an autosomal recessive inheritance characterized by markedly narrow ribs, micromelia, and multiple anomalies of major organs. We report a case of type IV SRPS with uncommon associations of polydactyly and bilateral polycystic kidneys, in a 28 week old female fetus. She was born dead to a 28 year old mother, showing a hydropic change, narrow thorax, and shortened limbs with postaxial heptasyndactyly of both hands and feet. Radiologic examination revealed short horizontal ribs, curved short tubular limb bones, small ilia and scapula, and a mild vertebral abnormality. Postmortem examination disclosed pulmonary hypoplasia, pancreatic cysts, hepatic fibrosis, and left persistent superior vena cava. In addition this case had bilateral huge polycystic renal dysplasia that was seldom described in any type of SRPS. Histologic sections of the vertebrae disclosed abnormal enchondral ossification with irregular and retarded hypertrophic zone.

Female

Characterization of a mitochondrial DNA deletion in patients with mitochondrial myopathy.

Kearns-Sayre syndrome (KSS) is the most commonly diagnosed mitochondrial myopathy and it produces severe neuromuscular symptoms. The most frequent cause is a mitochondrial DNA (mtDNA) deletion (common deletion) that removes a 4,977-bp segment of DNA that includes several genes encoding respiratory chain subunits. In this disorder, the population of deleted mtDNA molecules coexists with a population of normal, wild-type, full-length mtDNAs. We have performed a morphological study and a 3-primer polymerase chain reaction (PCR) on paraffin-embedded muscle tissues from two Korean KSS patients. Our results show that these patients have the essential clinical manifestations of KSS, as well as morphological evidence of mitochondrial myopathy. PCR analysis revealed the existence of two co-amplified fragments, the wild-type fragment having 152 bp and the deleted fragment having the 123 bp characteristic of common deletion. This study may provide valuable information for the molecular diagnosis of KSS in Koreans.

Adult

Quantitative analysis of mitochondrial DNA deletion in paraffin embedded muscle tissues from patients with KSS and CPEO.

The percentage of common deletion of mitochondrial DNA (mtDNA) was determined quantitatively by a PCR-based, non-radioactive method in DNA extracted from formalin-fixed, paraffin-embedded skeletal muscle tissues from two patients with Kearns Sayre syndrome (KSS) and one with chronic progressive external ophthalmoplegia (CPEO). The method involved PCR cycle titration of wild-type and deleted mtDNA in parallel, staining of gel bands with the sensitive fluorescence dye SYBR Green I, and quantitation of intensity on a computer screen by the NIH image program. We determined 75% and 71% common deletion of mtDNA in the KSS patients and 35% in the CPEO patient.

Adult

Central neurocytoma: the role of radiation therapy and long term outcome.

BACKGROUND: It has been suggested that the biologic behavior of central neurocytoma is indolent, although little is known regarding the role of radiation therapy and long term outcome. To clarify the role of radiation therapy and long term outcome, the authors retrospectively analyzed 15 cases of central neurocytoma. METHODS: Clinical records and radiologic findings of 15 cases of central neurocytoma diagnosed at Seoul National University Hospital between January 1982 and February 1995 were carefully reviewed. The duration of follow-up was from 18-168 months (mean, 52 months); follow-up images were reviewed and the patient's Karnofsky performance scale (KPS) was assessed up to the time of last follow-up. RESULTS: The age of the patients ranged from 15 to 60 years (mean, 25 years) and the male to female ratio was 11:4. Macroscopic total resection of the tumor was performed in seven patients, two of whom received fractionated radiation therapy. Subtotal removal of the tumor was performed in eight patients, five of whom received this same therapy. In 2 of the 5 patients who did not receive radiation therapy after macroscopic total resection, the tumors recurred 8 and 21 months after surgery, respectively; in contrast, recurrence was not detected in the 2 patients who received fractionated radiation therapy after macroscopic total resection. In all five patients who received fractionated radiation therapy after subtotal resection, the tumor shrank (n = 3) or disappeared (n = 2) during the postsurgical follow-up period ranging from 27-113 months; the tumor began to shrink from 6 months to 2 years after radiation. No change was found in the three patients who did not receive radiation therapy after subtotal resection. At the time of last follow-up, the KPS was greater than 90 in all patients except one who required assistance in his daily activities because of complications from radiation therapy. CONCLUSIONS: It is suggested that even if the biologic behavior of a central neurocytoma is benign, radiation therapy appears to have an effect on tumor control. However, it should be carefully decided whether to use radiation therapy for a residual tumor because radiation can cause delayed complications and the clinical course of subtotally resected patients who do not receive radiation therapy is extremely benign.

Activities of Daily Living

Abnormal expression of four novel molecular markers represents a highly aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23, erbB-2, and cathepsin D protein.

BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and cathepsin D are the most promising investigational prognostic factors in breast cancer. OBJECTIVES: The clinical utility of these molecular markers to predict recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast cancer patients were analyzed by immunohistochemical assay. Molecular biologic data were merged with clinicopathologic variables. RESULTS: Thirty-two patients (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72 months). Investigational factor expression had statistical correlation for recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%, three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis, lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of nm23 protein expression were significant variables to determine recurrence; in multivariate analysis, node status and tumor size emerged as the most significant variables for recurrence. CONCLUSIONS: Coexpression of the studied investigational variables functioned as significant prognostic correlates for recurrence. These findings suggest that the studied investigational prognostic factors possess the ability to discriminate a highly aggressive phenotype in breast cancer.

Biomarkers, Tumor

Mixed tumour of schwannoma and meningioma components in a patient with NF-2.

The authors present the case of an intracranial tumour consisting of both schwannoma and meningioma within the same tumour, in a patient with neurofibromatosis-2 (NF-2). A pre-operative diagnosis of this mixed tumour was not made. However, retrospectively, a meningiomatous area was found inside the acoustic neurinoma on magnetic resonance (MR) images. Predominant schwannoma with a minor component of meningioma was confirmed by histopathological and immunohistochemical examinations. The transitional zones of these two different tumours were macroscopically sharp but microscopically interdigitated. The patient had another meningioma and schwannoma in a separate section of the cranial cavity. Based on this patient, it is suggested that the collision of two kinds of tumours is the most likely hypothesis to explain the development of mixed components of schwannoma and meningioma within the same tumour.

Adolescent

High expression of tumor necrosis factor-alpha and interleukin-6 in periventricular leukomalacia.

OBJECTIVE: Periventricular leukomalacia, a common neonatal brain white matter lesion, is a major risk factor for cerebral palsy. Subclinical chorioamnionitis is a risk factor for the development of periventricular leukomalacia, and inflammatory cytokines have been implicated as central mediators of brain injury in this disorder. To elucidate the relationship between the local expression of cytokines and periventricular leukomalacia, we studied neonatal brains to determine whether high expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was observed in these lesions. STUDY DESIGN: Immunohistochemical staining for cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) was performed in 10% formalin-fixed, paraffin-embedded brain sections of 17 cases with periventricular leukomalacia. Specimens were obtained from autopsies performed between 1987 and 1994. Brain sections from 17 cases of neonatal deaths without periventricular leukomalacia lesions matched for gestational age at birth, duration of postnatal survival, and presence or absence of infection-related morbidity were used as controls. RESULTS: The expression of tumor necrosis factor-alpha, interleukin-1 beta, or interleukin-6 was demonstrated in 88% (15/17) of cases with and in 18% (3/17) of cases without periventricular leukomalacia (p < 0.001). Cytokines were expressed mainly in hypertrophic astrocytes and microglial cells. The expression of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 was identified in 82% (14/17), 29% (5/17), and 71% (12/17) of cases of periventricular leukomalacia, respectively. However, a significantly lower proportion of cases without periventricular leukomalacia expressed tumor necrosis factor-alpha (18%, 3/17) and interleukin-6 (6%, 1/17) than those with the disorder (p < 0.005 for each). CONCLUSIONS: Expression of tumor necrosis factor-alpha and interleukin-6 was observed more frequently in brain lesions with periventricular leukomalacia than in those without periventricular leukomalacia. These findings provide strong support for the hypothesis that proinflammatory cytokines play a role in the genesis of periventricular leukomalacia.

Brain Chemistry

Experimentally induced intrauterine infection causes fetal brain white matter lesions in rabbits.

OBJECTIVE: Periventricular leukomalacia, a common brain white matter lesion in preterm neonates, is a major risk factor for cerebral palsy. Epidemiologic studies have demonstrated an association between infection and periventricular leukomalacia. The purpose of this study was to determine whether ascending intrauterine infection could cause brain white matter lesions in the fetal rabbit. STUDY DESIGN: Rabbits with timed pregnancies underwent hysteroscopy at 20 to 21 days of gestation (70%). Animals were allocated in a ratio of 2:1 for inoculation with either Escherichia coli (0.2 ml containing 10(3) to 10(4) colony-forming units) or sterile saline solution. Both groups were treated with ampicillin-sulbactam (Unasyn, 100 mg/kg per day; Pfizer, Seoul) every 8 hours until they were killed 5 to 6 days after hysteroscopy. Histologic examination of the placentas and fetal brains was conducted. RESULTS: Forty-five animals underwent hysteroscopy; 31 were inoculated with E. coli and 14 with sterile saline solution. At the time the animals were killed, the rate of intrauterine infection was higher and there were fewer live fetuses in the E. coli-inoculated animals than in the saline solution group. Histologic evidence of brain white matter damage was identified in 12 fetuses born to 10 E. coli-inoculated rabbits but none in the saline solution group (p < 0.05). All rabbits with brain white matter lesions had evidence of intrauterine infection. Evidence of white matter damage included increased karyorrhexis, rarefaction, and disorganization of white matter. Apoptosis was demonstrated in areas of white matter damage by immunohistochemical studies. CONCLUSION: Experimental ascending intrauterine infection can cause fetal brain white matter lesions.

Animals

Congenital cystic adenomatoid malformation of the lung: CT-pathologic correlation.

OBJECTIVE: The purpose of this study was to correlate CT findings of congenital cystic adenomatoid malformation (CCAM) of the lung with pathologic findings. MATERIALS AND METHODS: CT scans of CCAM from 21 consecutive patients were analyzed retrospectively by two chest radiologists who achieved consensus. Pathologic findings were assessed by an experienced pulmonary pathologist. Preoperative CT findings were correlated with pathologic findings. RESULTS: Areas with small cysts (< 2 cm in diameter) were seen on CT scans in 19 (90%) of 21 patients, whereas areas with a large cyst (> 2 cm in diameter) were observed in 18 patients (86%). Areas of consolidation (n = 9; 43%) with heterogeneous attenuation on enhanced scans and areas of low attenuation (lower than normal lung) around cystic lesions (n = 6; 29%) were also seen on CT scans. The diameter of the largest cyst seen on CT scans in each patient ranged from 1.0 to 8.0 cm (median, 4.5 cm). Cysts that CT showed to be filled with air, fluid, or both correlated completely with the pathologic findings. Areas of consolidation corresponded histologically to areas of glandular or bronchiolar structures with or without areas of endogenous lipoid or organizing pneumonia or mucus plugs. Areas of low attenuation corresponded to areas of microcysts blended with normal lung parenchyma. CONCLUSION: CT scans show the variable internal characteristics of CCAM and can suggest the underlying pathology of such lesions.

Adolescent

In-vivo study on the harmful effect of the extremely low frequency unipolar pulsating magnetic field in mice.

We studied the biological effect of a magnetic field on murine brain and kidney. Magnetic field we used was generated by Magno-DR apparatus (Hanil Co., Korea) which produced a high density unipolar square pulsating magnetic field, about 0.3 approximately 0.5 Tesla at 7 Hertz. Animals were placed in the chamber of the machine for various times from 4 hours to 24 hours. Histological sections of brain and kidney were made after perfusion fixation with paraformaldehyde. The light microscopic examination showed eosinophilic change of cytoplasm and positive immunohistochemical reaction to amyloid precursor protein in the neurons of the cerebral cortex. However, the thalamus and brain stem were less affected. The changes in the brain was seen in the mouse exposed more than 12 hours. The renal tubular epithelium showed degenerated tubules scattered in cortical area but little change was noted in glomeruli in the cortex and collecting tubules in the medulla. Immunohistochemistry of the kidney showed weakly positive reaction for the amyloid precursor protein in the distal tubular epithelium after 4 hours of exposure. These data suggest that strong pulsating magnetic fields could induce deleterious effect on the murine brain tissue and renal cortical tubules.

Amyloid beta-Protein Precursor

Neonatal adenoviral pneumonia--report of three autopsy cases.

Adenovirus pneumonia, while common in infancy and childhood, is rarely documented but may be fatal in the neonatal period. In regard to the serious outcome and no responsiveness to common anti-viral agents, adenovirus infection should be considered in the differential diagnosis of pneumonia in neonates. We report three cases of fatal neonatal adenovirus pneumonia, all of which were diagnosed by postmortem examination. Two patients were born by cesarean section at 35 or 36 weeks of gestation, and the other was a 5100 gm postmature baby born by vaginal delivery at 43 weeks of gestation. Respiratory insufficiency was detected just after birth or in the immediate postnatal period, and was associated with lethargy and chest X-ray findings of pneumonic infiltration. The postmortem findings of these patients were remarkably consistent and characterized by predominant lung involvement. The lungs showed diffuse massive consolidation with scattered patchy hemorrhage, and histologically revealed multifocal necrotizing alveolitis and/or bronchiolitis, often with hemorrhage. Alveolar lining cells and desquamated cells contained numerous smudge ells and many cells with characteristic inclusion bodies. Electron microscopy revealed that these inclusion bodies consisted of arrays of icosahedral particles of adenovirus. It is unusual that one of the patients, who was born by cesarean section without any evidence of prenatal infection, developed adenoviral pneumonia; this indicates that infection may occur in the immediate postnatal period as well as during passage of the birth canal.

Adenoviridae Infections

Choroid plexus carcinoma in an infant.

Choroid plexus carcinoma is a rare tumor and has a strong tendency to spread along the cerebrospinal fluid pathway. The tumor frequently occurs in infants. Radiation therapy is not indicated in infants and the response of this tumor to chemotherapy is variable. Therefore, surgical removal plays a major role in the management of this tumor, especially in infants. A 2-month-old girl with an acute communicating hydrocephalus was presented. Through the left posterior parietal transcortical approach, a choroid plexus carcinoma which had poor demarcation from the posterior thalamus and the medial wall of the lateral ventricle was subtotally (> 95%) removed. Postoperatively a ventriculoperitoneal shunt was inserted. Chemotherapy was refused. Magnetic resonance imaging taken at 11 months after surgery showed multiple intracranial seeding of the tumor. She was in a bed-ridden state. This case revealed the aggressive behaviour of choroid plexus carcinoma in an infant and the dismal result of subtotal removal alone, though it is rather radical.

Choroid Plexus Neoplasms