Hyok-Hee Yoo

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Liver resection induces accelerated growth of residual hepatic micrometastases. Adjuvant chemotherapy may improve outcome if administered early after resection but may prove lethal if initiated prior to completion of DNA synthesis in regenerating liver. This study investigates phosphorus-31 nuclear magnetic resonance ((31)P-NMR) as a noninvasive tool for measuring energy changes reflective of hepatic DNA synthesis and for predicting safe timing of chemotherapy after 70% hepatectomy. To evaluate metabolic changes in regenerating liver, quantitative three-dimensional (31)P-NMR was performed, using the technique of chemical shift imaging at various time points after 70% hepatectomy in adult male Fischer rats. Animals receiving a course of 2'-deoxy-5-fluorouridine (FUDR; 100 mg/kg, i.p. four times per day x 5), initiated at the time of operation, were also evaluated to observe the effects of chemotherapy on liver regeneration. Forty-eight hours after resection, hepatic nucleoside tr...

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

This article presents the results of the Implementation Study of the Seoul Cancer Registry, which started in July, 1991 as a population based cancer registry in Seoul, Korea. The completeness and validity of the registered data were evaluated using Mortality/Incidence ratio (M/I ratio), Histologically Verified Cases (HV%), Primary Site Uncertain (PSU%), and Age Unknown (Age UNK%). Owing to the additional active surveillance, the completeness of the data turned out to be fairly acceptable, except for the aged over 75(Mortality/Incidence ratio was over 100%). Eventhough the Seoul cancer registry(SCR) has further way to go in the completeness especially among elderly persons, the validity of SCR data was also acceptable in terms of HV%, PSU%, and Age UNK%. However, PSU% and Age UNK% might need to be further reduced to be comparable with other well established cancer registries. The age standardized incidence rates(ASR) of all cancers between July 1, 1991 and June 30, 1992 were 232.4/100,000 in males and 147.9/100,000 in females. The top five major sites of cancers in Seoul were the stomach, liver, lung, colo-rectum, and bladder in order in males, and the uterine cervix, stomach, breast, colo-rectum, and liver in females. Those 5 cancer sites comprised 68.9% and 64.7% of the total cancer incidence in males and females, respectively.

PURPOSE: To determine the prevalence of testicular microlithiasis in patients who were referred for scrotal ultrasonography (US) at a tertiary care cancer center and to evaluate the association between microlithiasis and cancer. MATERIALS AND METHODS: Testicular ...

To determine the etiology of pulmonary nodules resected at video-assisted thoracoscopic surgery (VATS) and establish the probabilities that single or multiple nodules resected at VATS represent malignancy in patients with or patients without known cancer. Pathology reports from VATS performed between January 1995 and July 1997 were searched for data on gross specimens revealing pulmonary nodules 3 cm or smaller. Findings were correlated with clinical and histologic data. In 254 patients with one nodule resected at VATS, the nodules were malignant in 108 patients with and in 32 patients without known cancer (P < .03). Among 172 patients with multiple nodules resected, at least one nodule was malignant in 85 patients with and in 20 patients without known cancer (P > .05). Nodules larger than 1 cm were more likely to be malignant than were smaller nodules (P < .002). In patients with known malignancy, nodules smaller than 0.5 cm were more likely to be benign, whereas nodules larger than 0.5 cm but smaller than 1 cm were more likely to be malignant (P < .001). A single pulmonary nodule resected at VATS was more likely to be malignant in patients with known cancer. Nodules larger than 1 cm but smaller than 3 cm resected at VATS were more likely to be malignant. Nodules smaller than 0.5 cm were more likely to be benign.

The brain-derived neurotrophic factor (BDNF) gene is a plausible candidate for early-emerging negative emotionality (NE), and evidence suggests that the effects of this gene may be especially salient in the context of familial risk for child maladjustment. We therefore examined whether the single-nucleotide polymorphism producing a valine-to-methionine substitution at codon 66 (val66met) of the BDNF gene was associated with childhood NE, in the context of parental depression and relationship discord. A sample of 413 three-year-old children was assessed for NE using standardized laboratory measures. The children's parents completed clinical interviews as well as a measure of marital satisfaction. Children with at least one BDNF methionine (met) allele exhibited elevated NE when a parent had a history of depressive disorder or when relationship discord was reported by a parent. In contrast, this allele was associated with especially low NE when parental depression was absent and when the parental relationship was not discordant. Our findings suggest that the BDNF met allele confers increased child sensitivity to both positive and negative familial influences.

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated β-galactosidase (SA-β-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro. We demonstrated the beneficial tumor suppressive role of ionizing radiation (IR)-induced premature senescence in vitro and in vivo. FR inhibited tumor growth via induction of premature senescence as effectively as an equivalent SR dose (≥6 Gy). In addition, CD and eEF1 were valuable biomarkers of cellular senescence in either SR- or RF-exposed carcinoma cells or xenograft mice. Our results suggest that 2 Gy of a conventional RT regime could achieve a better clinical outcome if premature senescence could be increased through an improved understanding of its molecular action mechanism.

Phosphorus metabolites in the jaundiced rat liver were studied by three-dimensional phosphorus chemical shift imaging (CSI). Animals were studied at 1, 2, and 3 weeks post-ligation of the common bile duct. Quantitation of metabolites was performed using an external standard. Metabolite T(1) values were assessed in CSI experiments on normal untreated animals. High-performance liquid chromatography (HPLC) was used to measure adenine nucleotides in a separate group of jaundiced rats. 3D-CSI did not detect significant changes in NTP in jaundiced animals relative to baseline controls. At two and three weeks post bile duct ligation, pH was significantly elevated. HPLC data comparing ATP levels to baseline controls also detected no change except for elevated ATP detected on Day 21. (31)P NMR chemical shift imaging may be used to assess liver metabolites under conditions of stress such as jaundice. However, absolute quantitation requires careful attention to many factors including point spread function, correct T(1) values, and adequate signal-to-noise ratio.