An autopsy case of congenital tuberculosis is described in a 41-day-old female infant who was born to a mother having active pulmonary tuberculosis. The primary complex was seen in the liver and portal lymph nodes, and there was a generalized miliary dissemination including lung, liver, spleen, pancreas, adrenals, thyroid, thymus, kidneys, brain, and bowel. The organism was confirmed to be Mycobacterium tuberculosis. The tubercles were histopathologically of various chronicity and characterized by massive caseation and fairly poor peripheral lymphohistiocytic reaction. Giant cell response was also minimal. It should be stressed that although rare, tuberculosis is still an important disease in Korea that can involve fetus or newborn infants if pregnant women are untreated or unnoticed for her tuberculosis.
Female ; Humans ; Infant, Newborn ; Mycobacterium tuberculosis/isolation & purification ; Organ Specificity ; Postmortem Changes ; Tuberculosis, Pulmonary/*congenital/diagnosis/pathology

We experienced a case of chronic fibrosing pancreatitis in an 18/12-year-old girl, which was idiopathic because there were no familial back ground, no cystic fibrosis of pancrease, no ductal anomalies and obstruction. The patient presented intermittent colicky abdominal pain and progressive obstructive jaundice, but T-tube drainage and removal of the lymph nodes around the common bile duct relieved her symptoms and disease process. This seems to be the first case reported in a Korean child. Idiopathic fibrosing pancreatitis should be considered in the differential diagnosis of abdominal pain with obstructive jaundice in children.
Abdominal Pain/complications ; Female ; Fibrosis ; Humans ; Infant ; Jaundice, Chronic Idiopathic/complications ; Pancreatitis/complications/*pathology

Five thyroid carcinomas showing clinically aggressive biologic behavior were retrospectively reviewed to evaluate the possible presence of morphologic differences from conventional thyroid carcinomas. They were originally diagnosed as follicular carcinomas, medullary carcinoma, papillary carcinoma, and mixed papillary and medullary carcinoma. There were three males and two females. The age at the time of initial diagnosis ranged from 36 years to 67 years (mean 56 years). The size of the tumor varied from 4.5cm to 10cm (mean diameter 7cm). One patient died of brain metastasis four years after the initial therapy and the other four patients are still alive with local recurrences and/or metastases to bone, spinal cord, lung, and buttock. Histologically these lesions are categorized into two different groups: insular variant and columnar cell variant. Insular variant was characterized by well-defined nests (insulae) that are composed of small, uniform cells, frequent tumor necrosis, and hyalinization of the stroma. Columnar cell variant was characterized by tall columnar cells with marked nuclear statification. All five cases stained positively for thyroglobulin and negatively for calcitonin. With the above clinical and histopathological findings, we interpreted these lesions as a poorly differentiated carcinoma, biologically in an intermediate position between well differentiated and anaplastic carcinomas. The rapid and often fatal outcome associated with these variants of poorly differentiated carcinoma warrants aggressive treatment at the time of diagnosis.
Adenocarcinoma/*pathology/secondary ; Adult ; Carcinoma, Papillary/*pathology/secondary ; Evaluation Studies as Topic ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Thyroid Neoplasms/*pathology/secondary ; Tumor Cells, Cultured

For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively.
Administration, Oral ; Humans ; Isoniazid/*cerebrospinal fluid ; Metabolic Clearance Rate ; Models, Biological ; Tuberculosis, Meningeal/*cerebrospinal fluid

To determine the content of thyroglobulin in oxyphilic cells of the thyroid, which have been considered as non-thyroglobulin producing cells, the degree of stainability of the various oxyphilic cells for thyroglobulin was compared with that of non-oxyphilic follicular cells in either same or different lesion. A total of 13 oxyphilic lesions, including three follicular adenomas containing oxyphilic cell nodules, four pure oxyphilic cell adenomas, and six Hashimoto's thyroiditis were compared with 16 of non-oxyphilic lesions such as, seven follicular adenomas, four chronic lymphocytic thyroiditis, and five Graves' disease. Many oxyphilic cells stained positively for thyroglobulin regardless of their morphologic variation, but less intensely than the usual follicular cells in follicular adenomas, chronic lymphocytic thyroiditis, and Graves' disease. The stainability of oxyphilic cells for thyroglogulin did not show any significant correlation with morphologic features, whereas in follicular adenomas, the non-oxyphilic follicular cells forming microfollicles stained less strongly for thyroglobulin than the same cells lining large mature follicles in a reproducible way. With above findings, we concluded that oxyphilic cells maintain the functional activity in terms of thyroglobulin synthesis, although the content of the thyroglobulin is less than that of non-oxyphilic colloid forming follicular cells.
Adenoma/*metabolism/pathology ; Graves Disease/*metabolism/pathology ; Humans ; Staining and Labeling ; Thyroglobulin/*biosynthesis ; Thyroid Neoplasms/pathology ; Thyroiditis, Autoimmune/*metabolism/pathology

We adapted one of the in-vitro immunization methods to induce antibody responses and confirmed the success of the immunization by enzyme-linked immunosorbent assay (ELISA) without hybridization. We have previously reported several methods of in-vitro immunization using different conditioned media. Here we introduce another method of in-vitro immunization using a mixture of three types of supernatant (thymocytes, and adherent and non-adherent splenocytes of mouse). Splenocytes were immunized in-vitro by a recombinant human growth hormone (rhGH) with the above conditioned media, and the results by ELISA showed a much higher optical density than the other in-vitro immunization methods that we had previously reported. Humoral responses as a result of in-vitro immunization to soluble antigens were easily confirmed by ELISA using the above-conditioned media. This finding indicates that any other conditions thought to be critical by other researches may not be essential for in-vitro immunization.
Animals ; *Antibody Formation ; Antigens/immunology ; Cell Adhesion ; Female ; Growth Substances/*immunology ; Immunization ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/immunology ; Spleen/cytology/*immunology ; T-Lymphocytes/*immunology

Recurrent alternating stroke, i.e., one time ischemic and the other hemorrhagic or vice versa, is an uncommon event. We report a series of eight patients who had recurrent alternating strokes, which were diagnosed by CT scans during the last four years. Infarcts preceded hemorrhage in six patients. In the remaining two patients, hemorrhage developed first and infarct followed. All ischemic strokes were the lacunar infarcts. The lesions of the two attacks were located in different sites in all cases except one. The mean age of the patients was 56.6 years at the time of the first attack and 57.5 years at the time of the second. The mean interval between attacks was 11.8 months. All patients were hypertensive on admission. After the first attack, the outcome was favorable in all patients. However, after the second attack the outcome deteriorated to moderate disability in three, severe disability in one and death in four. We discuss some possible reasons for the rarity of recurrent alternating stroke.
Brain Ischemia/*complications ; Cerebral Hemorrhage/*complications ; Cerebrovascular Disorders/*radionuclide imaging ; Female ; Humans ; Hypertension/complications/radionuclide imaging ; Male ; Middle Aged ; Prognosis ; Recurrence ; Tomography, X-Ray Computed

EGFR and KRAS mutations are two of the most common mutations that are present in lung cancer. Screening and detecting these mutations are of issue these days, and many different methods and tissue samples are currently used to effectively detect these two mutations. In this study, we aimed to evaluate the testing for EGFR and KRAS mutations by pyrosequencing method, and compared the yield of cytology versus histology specimens in a consecutive series of patients with lung cancer. We retrospectively reviewed EGFR and KRAS mutation results of 399 (patients with EGFR mutation test) and 323 patients (patients with KRAS mutation test) diagnosed with lung cancer in Konkuk University Medical Center from 2008 to 2014. Among them, 60 patients had received both EGFR and KRAS mutation studies. We compared the detection rate of EGFR and KRAS tests in cytology, biopsy, and resection specimens. EGFR and KRAS mutations were detected in 29.8% and 8.7% of total patients, and the positive mutation results of EGFR and KRAS were mutually exclusive. The detection rate of EGFR mutation in cytology was higher than non-cytology (biopsy or resection) materials (cytology: 48.5%, non-cytology: 26.1%), and the detection rate of KRAS mutation in cytology specimens was comparable to non-cytology specimens (cytology: 8.3%, non-cytology: 8.7%). We suggest that cytology specimens are good alternatives that can readily substitute tissue samples for testing both EGFR and KRAS mutations. Moreover, pyrosequencing method is highly sensitive in detecting EGFR and KRAS mutations in lung cancer patients.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/genetics/metabolism/*pathology ; DNA Mutational Analysis ; DNA, Neoplasm/chemistry/metabolism ; Female ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Middle Aged ; Mutation ; Receptor, Epidermal Growth Factor/*genetics/metabolism ; Retrospective Studies ; ras Proteins/*genetics/metabolism

Orthodenticlehomeobox 1 (OTX1) overexpression had previously been associated with the progression of several tumors. The present study aimed to determine the expression and role of OTX1 in human hepatocellular carcinoma (HCC). The expression level of OTX1 was examined by quantitative real-time PCR (qRT-PCR) in 10 samples of HCC and paired adjacent non-cancerous tissues, and by immunohistochemistry (IHC) analysis in 128 HCC samples and matched controls. The relationship between OTX1 expression and the clinicopathological features werealso analyzed. Furthermore, the effects of OTX1 knockdown on cell proliferation and migration were determined in HCC cell lines. Axenograft mouse model was also established to investigate the role of OTX1 in HCC tumor growth. TheqRT-PCR and IHC analyses revealed that OTX1 was significantly elevated in HCC tissues compared with the paired non-cancerous controls. Expression of OTX1 was positively correlated with nodal metastasis status (P = 0.009) and TNM staging (P = 0.001) in HCC tissues. In addition, knockdown of OTX1 by shRNA significantly inhibited the proliferation and migration, and induced cell cycle arrest in S phase in vitro. Tumor growth was markedly inhibited by OTX1 silencing in the xenograft. Moreover, OTX1 silencing was causable for the decreased phosphorylation level of ERK/MAPK signaling. In conclusion, OTX1 contributes to HCC progression possibly by regulation of ERK/MAPK pathway. OTX1 may be a novel target for molecular therapy towards HCC.
Aged ; Animals ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/*pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Liver/metabolism/pathology ; Liver Neoplasms/metabolism/*pathology ; Lymphatic Metastasis ; MAP Kinase Signaling System ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Neoplasm Staging ; Otx Transcription Factors/antagonists & inhibitors/genetics/*metabolism ; Phosphorylation ; RNA Interference ; Real-Time Polymerase Chain Reaction ; S Phase Cell Cycle Checkpoints ; Transplantation, Heterologous

Glioblastoma (GBM) can be classified into molecular subgroups, on the basis of biomarker expression. Here, we classified our cohort of 163 adult GBMs into molecular subgroups according to the expression of proteins encoded by genes of alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase (IDH) and TP53. We focused on the survival rate of molecular subgroups, depending on each and various combination of these biomarkers. ATRX, IDH1 and p53 protein expression were evaluated immunohistochemically and Kaplan-Meier analysis were carried out in each group. A total of 15.3% of enrolled GBMs demonstrated loss of ATRX expression (ATRX-), 10.4% expressed an aberrant IDH1 R132H protein (IDH1+), and 48.4% exhibited p53 overexpression (p53+). Survival differences were statistically significant when single protein expression or different combinations of expression of these proteins were analyzed. In conclusion, in the case of single protein expression, the patients with each IDH1+, or ATRX-, or p53- GBMs showed better survival than patients with counterparts protein expressed GBMs. In the case of double protein pairs, the patients with ATRX-/p53-, ATRX-/IDH1+, and IDH1+/p53- GBMs revealed better survival than the patients with GBMs with the remained pairs. In the case of triple protein combinations, the patients with ATRX-/p53-/IDH+ showed statistically significant survival gain than the patients with remained combination of proteins-expression status. Therefore, these three biomarkers, individually and as a combination, can stratify GBMs into prognostically relevant subgroups and have strong prognostic values in adult GBMs.
Adult ; Aged ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/*diagnosis/metabolism/mortality ; DNA Helicases/*metabolism ; Disease-Free Survival ; Glioblastoma/*diagnosis/metabolism/mortality ; Humans ; Immunohistochemistry ; Isocitrate Dehydrogenase/*metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Nuclear Proteins/*metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics/*metabolism ; Young Adult