Postmor tem next-generation sequencing (NGS) plays a crucial role in uncovering previously unidentified genetic causes of death. It provides essential findings useful for counseling affected family members and advancing our understanding of genetic diseases. In this report, we present the first documented autopsy case of hypertrophic cardiomyopathy (HCM) in South Korea in which postmortem NGS was used to identify a novel mutation. A 40-year-old male with no relevant medical history experienced sudden death at home. The autopsy revealed cardiac findings consistent with HCM but no other potential causes of sudden death. Through postmortem NGS analysis, a novel pathogenic mutation, c.2833_2834del, in MYBPC3 gene, was discovered; hence, this serves as the first report of this mutation in a Korean population. This finding not only confirms the diagnosis of HCM but also provides a plausible explanation for the sudden death. Given the hereditary nature of HCM, genetic counseling is strongly recommended, especially for the deceased’s nine-year-old son, who has a 50% risk of inheriting the mutation. This case underscores the critical role of postmortem NGS in the field of forensic medicine. The significance of NGS and necessity for integration into autopsy investigations are highlighted.

Background: Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology. Methods: We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding. Results: Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis. Conclusions Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

BACKGROUND AND OBJECTIVES: P1-N1-P2 complex reflecting pre-attentive processing of sound presents several temporally overlapping and spatially distributed neural sources in or near primary auditory cortex. This study investigated cortical evoked responses to the P1-N1-P2 complex to determine the perceptual contributions of the acoustic features. SUBJECTS AND METHODS: Eleven young native-speaking Korean adults with normal hearing participated. The stimuli were three bilabial, three alveolar, and three velar syllables, and each place of articulation had one lax, one tense, and one aspirate syllable as the manner of articulation. RESULTS: The results indicate the cortical responses to the velar syllables significantly differed from the bilabial and alveolar groups at the P1-N1 and N1-P2 interamplitude. However, there is no significant difference in the cortical responses between Korean lax and tense syllables, which is significant for English phonology in terms of voice onset time. Further, the cortical responses to aspirate syllables significantly differed from two other groups in the interamplitude, demonstrating that the /tha/ syllable had the largest response at N1-P2 interamplitude. CONCLUSIONS: Different speech sounds evoked different P1-N1-P2 patterns in the place and the manner of articulation in terms of interamplitude, but not of the latency and interlatency although further studies should be followed.
Acoustics ; Adult ; Auditory Cortex ; Hearing* ; Humans ; Phonetics ; Speech Perception ; Transcutaneous Electric Nerve Stimulation ; Voice

Stress induces degeneration of brain structures and functions. Particularly, hippocampus is sensitive to stressful stimulations. In the present study, the change of synaptic related molecules in the mouse dentate gyrus was examined with immunohistochemistry after restraint stress. We subjected mice to restraint stress for 6 h per day for 4 days. As a result, the number of Ki-67, a marker for proliferation, and doublecortin (DCX), a marker for neurogenesis, immunoreactive cells was decreased in the stress group. On the other hand, the intensity of calbindinD-28k, a marker of pre-existing granule cells, immunoreactivity was increased in the granule cell layer after 4 days restraint stress. As well as, the immunoreactivity of synaptic related molecules, postsynaptic density-95 (PSD-95), growth association protein-43 (GAP-43) and beta-NADPH-d reactivity were increased in the inner molecular layer of dentate gyrus after 4 days restraint stress. In conclusion, this study shows that repeated restraint stress suppresses neurogenesis in dentate gyrus and strengthens synaptic plasticity of existing granule cells.
Animals ; Brain ; Dentate Gyrus* ; Hand ; Hippocampus ; Immunohistochemistry ; Mice* ; Neurogenesis ; Plastics*

PURPOSE: Medullary thyroid cancer (MTC) is a rare disease and the clinical course of MTC many vary. In this study, we analyzed the factors influencing the prognosis of MTC. METHODS: The study group consisted of 37 patients with MTC seen at KNUH between July 1985 and July 2003. We analyzed the medical records of MTC surgical cases in a retrospective study to analyze treatment results and utilized the Kaplan-Meier and chi-squred tests to determine the correlation of prognosis and recurrence. RESULTS: The median age of patients was 39 years and 7 patients had a family history and accompanying disease. No metastases were detected at the time of diagnosis. The majority of the sizes of tumors were under 4 cm in 22 cases and 24 cases (64.9%) showed unilateral tumor locations. Twenty cases (48.6%) showed lymph node metastasis, and invasion of the surrounding organs was seen in 5 cases (13.5%) of these cases. A total thyroidectomy and central neck dissection was performed in all cases. In 17 cases, a modified radical neck dissection was performed initially. Recurrence was detected in 13 out of 37 cases. The most common site of recurrence was the neck, followed by the lung and liver. We analyzed the factors that affected recurrence and it was found that lymph node metastasis and the TNM stage had a statistically significant relationship. No factor showed relevance to prognosis by multivariate analysis. The survival rates were 89.2% for 5 years and 83.8% for 10 years. CONCLUSION: We could not find any statistical significance for a factor relevant to the prognosis of the patients by multivariate analysis. However, as the 10 year-survival rate was 83.8%, we can expect improvement in the treatment of MTC with surgical management (total thyroidectomy and central neck dissection) and constant follow-up.
Diagnosis ; Follow-Up Studies ; Humans ; Liver ; Lung ; Lymph Nodes ; Medical Records ; Multivariate Analysis ; Neck ; Neck Dissection ; Neoplasm Metastasis ; Prognosis ; Rare Diseases ; Recurrence ; Retrospective Studies ; Survival Rate ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

Voluntary running is known to dramatically increase the cell proliferation and neurogenesis in the dentate gyrus of the adult mouse hippocampus. However, it is crucial to realize that adding excitatory neurons could result in serious maladaptive outcomes for hippocampal circuit function. To investigate the response of mature granule cells on the increase of cell proliferation during voluntary running, we investigated the temporal change of calbindin-D28k (a marker for mature granule cells) using immunohistochemistry during voluntary running with upregulated neurogenesis. By using immunohistochemsitry for Ki-67 and doublecortin (DCX), we observed that the cell proliferation and differentiation of granule cells increased at 1 week of voluntary running. We found that, at 6 weeks of voluntary running, the cell proliferation and differentiation of granule cells returned to sedentary control levels. On the other hand, calbindin-D28k immunoreactivity decreased in the granular cell layer of the dentate gyrus and CA3 region of hippocampus after 1 week of voluntary running. At 6 weeks of voluntary running, the density of the calbindin-D28k in the granular cell layer and CA3 region was returned to the sedentary control level. These results demonstrate that the cell proliferation and differentiation are increased at early point of voluntary running, and the granule cell activity in the dentate gyrus is temporally changed for response to the increase of cell proliferation and differentiation during voluntary running.
Adult ; Animals ; Calbindin 1* ; Cell Proliferation ; Dentate Gyrus* ; Hand ; Hippocampus ; Humans ; Immunohistochemistry ; Mice* ; Neurogenesis ; Neurons ; Running*

We found that the expression and activity of endothelial nitric oxide synthase (eNOS) is increased in the hippocampus during exercise (Moon et al., 2006). However, the upstream regulatory factor on the eNOS expression in the hippocampus during exercise has not been clear. In this study, we investigate the role of acetylcholine (ACh) as a regulatory factor for the eNOS expression and activity in the hippocampus during exercise. The results of the present study demonstrate that voluntary wheel running exercise for two weeks increases the expression and activity eNOS. In addition, choline acetyltransferase (ChAT) immnunoreacitvity within the hippocampus was increased after 2 weeks exercise. We further found that the upregulation of ACh with treatment of physostigmine, a booster of ACh releasing, increase the expression and activity of eNOS in the hippocampus. This present study provides the evidence that the upregulation of eNOS during exercise may be mediated by ACh in the hippocampus.
Acetylcholine ; Choline ; Choline O-Acetyltransferase ; Hippocampus ; Nitric Oxide Synthase Type III ; Physostigmine ; Running ; Up-Regulation

Background: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate. Methods: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion. Results: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised. Conclusions Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.