BACKGROUND: In this study, we investigated the early time course of expression of the major histocompatibility (MHC) antigens, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). MATERIAL AND METHOD: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7 (group 1, n=6), 15 (group 2, n=6), 21 (group 3, n=6), and 30 (group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. RESULT: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels (vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. CONCLUSION: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.
Allergy and Immunology ; Allografts ; Animals ; Atherosclerosis ; Coronary Vessels* ; Endothelial Cells ; Heart* ; Histocompatibility ; Histocompatibility Antigens ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Mice* ; Microscopy ; Transplantation ; Tropomyosin ; Vascular Cell Adhesion Molecule-1

Two dimensional alignment of valves in the cardiac skeleton is studied using 49 fetal hearts. They are standardized with fixed length between the centers of mitral and tricuspid valves. The relations among the parameters and of wall thichness ratio are studied, especially by the change of gestational age, mitral aortic distance and pulmonary-aortic distance, the angles between the two lines and mitral-tricuspid line. Anterior shift of great vessels was seen in heart with gestational age less than 20 weeks. Long mitral-aortic distance showed anterior shift of the great arteries and left ventricle was relatively thicker than right ventricle. Narrow aortomitral-tricuspid angle denoted posterior shift of great vessels and thich right ventricle. Short pulmonary-aortic distance denoted antero-posterior alignment and posterior shift of the vessels and thick left ventricle. Left-right alignment of vessels was not associated with right-ward shift but only with pulmonic displacement to the left. By these observation abnormal alignment of valves in cardiac skeleton would be a basic defect in bulboventricular malformation and we could find basic difference of cardiac skeleton, between normal variation and abnormal heart.
Humans

Owing to recent advancements in next-generation sequencing and bioinformatics, genetic data of urological malignancies exponentially studied and published. Application of precision medicine strategies for cancer diagnosis, management is just around the corner, and we need to prepare for this paradigm change. For this reason, we performed the literature reviews of 13 landmark studies for urological malignancies, 5 for prostate cancer, 5 for renal cell carcinoma, and 3 for urothelial carcinoma. Furthermore, we reviewed potentially druggable genes for urological malignancies that have in vivo/in vitro evidence. Finally, we selected total 255 genes included important mutations, structural variations, copy number alterations, clinically informative genes and potential drug target genes for prostate cancer, renal cell carcinoma, and urothelial carcinoma. This literature review and comprehensive molecular characterization of urological malignancies make help to understanding genetic backgrounds of the disease. However, there was less than 5% of Asian data included in current landmark studies for urological malignancies; thus we need to build up the large-scaled genetic studies for Korean population.

Spondylometaphyseal dysplasia (SMD) is an extremely rare, which affects the spine and metaphy-ses of the tubular bones on terms of enchondrogenesis. Children who had Kozlowski dwarfism, type of SMD are not recognized until they reach school age since they have normal clinical feature, weight and size in early childhood. Authors experienced a typical case of Kozlowski type of SMD in a 10 years old male who had i) generalized platyspondyly with anterior tapering of vertebrae ii) generalized metaphyseal dysplasia iii) minimal changes in the carpal and tarsal bones. This case is to be reported with review of references.
Child ; Dwarfism ; Humans ; Male ; Spine ; Tarsal Bones

The congenital renal cystic disease encompasses a complex group of pathologic and clinical entities. We retrospectively reviewed 42 cases of congenital renal cystic lesions classified into four Potter types in a series of 2,063 consecutive autopsies from 1981 to 1996. According to our study based on morphologic, clinical, genetic features and associated anomalies, type I and III are relatively compatible with Potter's original definition. However, it was reasonable that type II and IV are classified to the same group because of: 1) very similar histologic findings representing dysplastic kidney, 2) many associated anomalies, 3) no evidence of inheritance, and 4) presence of a combined type. Syndrome associated cysts, such as Meckel-Gruber syndrome, were also separately classified. If the dysplastic evidence was insufficient for diagnosis to the dysplastic kidney in type II and IV, then these cases would be better classified into a cystic disease associated with congenital hydronephrosis. We propose a classification of the congenital cystic disease of the kidney to be: 1) dysplastic kidney, 2) cystic disease associated with congenital hydronephrosis, 3) polycystic kidney, and 4) syndromic cystic disease.
Autopsy ; Classification* ; Diagnosis ; Hydronephrosis ; Kidney* ; Polycystic Kidney Diseases ; Retrospective Studies ; Wills

PURPOSE: Total prolapse of internal hemorrhoids around the entire anal circumference still remains as a challenging problem. Whitehead's circumferential hemorrhoidectomy is one of the surgical options. To elucidate efficacy of Whiteheads operation, we analyzed the surgical outcomes of Whiteheads operation. METHODS: The medical records of 165 consecutive patients who underwent Whiteheads operation for end-stage hemorrhoids were retrospectively reviewed. The mean operation time, the mean blood loss, and the mean hospital stay were examined. Also the types of complications were identified. All patients were followed for extended periods and in May 2003 they were asked to appraise their satisfaction (mean follow-up duration was 45.5 months, 12~93 month range). RESULTS: The mean operation time was 21.5+/-5.3 minutes, the mean blood loss was 50.5+/-22.0 cc, and the average hospital stay was 5.5+/-1.5 days. Early postoperative complications were fecal incontinence (60.6%) and voiding difficulty (53.3%). These problems were spontaneously resolved within 2 weeks. Pain was the most difficult problem, and all patients required a parenteral opioid for relief of pain. The only late complication was anal stenosis. Objectively, anal stenosis was found in 66 patients; however, 22 patients (13.3%) complained of defecation difficulty. Among them, only 4 patients required surgical treatment. The average score of satisfaction according to the patients themselves was 4.0+/-2.2, 0 being no satisfaction and 5 being complete satisfaction. CONCLUSIONS: The Whitehead operation, if performed properly for the selected patients, still remains as one of the best surgical options for end-stage hemorrhoids.
Constriction, Pathologic ; Defecation ; Fecal Incontinence ; Follow-Up Studies ; Hemorrhoidectomy ; Hemorrhoids ; Humans ; Length of Stay ; Medical Records ; Postoperative Complications ; Prolapse ; Retrospective Studies

PURPOSE: Thymidylate synthase (TS) expression in colorectal cancer is regarded as both a prognostic marker and a predictor of response to fluoropyrimidine-based therapies targeting TS. However, results from immunohistochemical staining of TS show wide discrepancies. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with operable colorectal cancer treated by a curative resection. METHODS: The cases of 121 patients with stage II or III colorectal cancer, who underwent a curative resection, were reviewed. After DNA extraction from paraffin- embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction. RESULTS: Sixty-eight subjects were homozygotes for the triple repeat variant (group A, L/L, 250-bp), and 53 subjects (group B) were either homozygotes for the double repeat variant (S/S, 220-bp) or heterozygotes (S/L, 220 and 250- bp). The difference between stage II and stage III patients was significant with regard to the 5-year actuarial survival (87% vs 63%, P=0.0320). Examining the survival according to the TS polymorphism, we found a significant difference between group A and B (80% vs 53%, P=0.0481). In patients with stage II disease, the difference in survival rates between group A and B did not reach statistical significance (43% vs 86%, P=0.1678). However, the difference was significant between group A and B for stage III disease (77% vs 41%, P=0.0414). CONCLUSIONS: We found the TS polymorphism to be a significant and independent prognostic factor for operable colorectal cancer. We think assay of the TS polymorphism can overcome the technical pitfalls of immunohistochemical staining and give more solid prognostic information in the treatment of colorectal cancer.
Colorectal Neoplasms* ; DNA ; Heterozygote ; Homozygote ; Humans ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Survival Rate ; Tandem Repeat Sequences ; Thymidylate Synthase*

Clear cell renal cell carcinoma (ccRCC) is a disease with a wide variety of clinical progressions such as the rate of disease progression or the degree of metastasis. About 30% of ccRCC patients suffer from metastatic diseases, and about 30% develop metastasis after diagnosis. In the case of metastatic RCC, early prediction of the disease is important because of the poor prognosis, but ccRCC-specific molecular markers for clinical use are not available yet. As an alternative, liquid biopsy, which can find molecules released from tumor tissues in circulating blood and obtain information on metastatic dissemination and recurrence of ccRCC, is emerging. In this article, we will introduce molecules such as cell free DNA, cell free RNA, protein, and exosomes available as circulating biomarkers for liquid biopsy. We will also introduce some promising technologies that can compensate for the limitations of liquid biopsy.

Objective: 68 Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N’,N’’-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68 Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68 Ga-NGUL in healthy volunteers and the lesion detection rate of 68 Ga-NGUL in patients with prostate cancer. Materials and Methods: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68 Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68 Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. Results: All 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68 Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68 Ga-NGUL PET/CT or conventional imaging. Among them, 68 Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. Conclusion 68 Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68 Ga-NGUL is a valuable option for prostate cancer imaging.

PURPOSE: S100B protein is widely used as a measure of glial activity or damage in several brain conditions. Central nervous system (CNS) infections can cause neurological sequelae because of parenchyma invasion. It is difficult to predict further neuronal damage in the CNS infection. The present study is aimed to evaluate the role of the cerebrospinal fluid (CSF) S100B protein as an indicator of neuronal damage in CNS infection. MATERIALS AND METHODS: We measured the concentration of CSF S100B protein in 62 patients with a CNS infection using an Enzyme-Linked Immunosorbent Assay. The patients with CNS infections were classified as having no neuronal damage (CNS-N) or as having neuronal damage (CNS+N) according to the presence of neurological change or structural lesions on brain MRI. RESULTS: The CSF S100B protein level of the CNS+N group (n=22, 0.235 microg/L, 0.10-2.18) was significantly higher than that of the CNS-N group (n=40, 0.087 microg/L, 0.06-0.12) and control group (n=40, 0.109 microg/L, 0.07-0.14, p<0.01). Using an arbitrary cut off value, S100B-positive CSF was detected in 2.5% of the CNS-N group and in 50% of the CNS+N group (p<0.05). CONCLUSION: These findings suggest that increased S100B protein levels in the CSF may be associated with the neuronal damage following CNS infections.
Adolescent ; Adult ; Aged ; Brain/pathology ; Central Nervous System Infections/cerebrospinal fluid/*pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; S100 Calcium Binding Protein beta Subunit/*cerebrospinal fluid