Transforming growth factor (TGF)-beta1 plays an important role in hepatocarcinogenesis and has been described as a useful tumor marker and one of the poor prognostic indicators in patients with hepatocellular carcinoma (HCC). To investigate the role and cellular localization of TGF-beta1 during multistep hepatocarcinogenesis we performed a quantitative analysis of TGF-beta1 mRNA and immunohistochemical expression of TGF-beta1 and TGF-beta receptor II (TGF-betarII) in female Sprague-Dawley rats. The experimental groups included neoplastic lesions produced by Solt-Farber's protocol, regenerating liver after partial hepatectomy, and normal control. Quantitative change of TGF-beta1 mRNA was analysed by competitive reverse-transcription polymerase chain reaction (RT-PCR). TGF-beta1 protein and TGF-betarII expression were evaluated by immunohistochemical stain. The discrete tumor nodules were detected on 14th day and then increased in number and size. Three HCCs were induced on 8th or 9th month. RT-PCR demonstrated TGF-beta1 mRNA band in all examples of the normal and regenerating liver, nodules and HCCs. Competitive RT-PCR displayed higher TGF-beta1 mRNA in nodules, HCCs and regenerating liver than in normal controls. Hepatocytes from control and regenerating livers showed weak immunoreactivity for TGF-beta1. In contrast, the cytoplasm of hepatocytes of nodules in 7th, 8th and 9th month and HCCs were intensely stained for TGF-beta1. Some sinusoidal cells showed immunoreactivity for TGF-beta1 in all experimental groups. In early phase of carcinogenesis, the cytoplasm of hepatocytes in liver of 12h, 1d and 3d showed transiently increased immunoreactivity for TGF-beta1 and The immunoreactivity decreased thereafter. TGF-beta1 mRNA was also detected in the neoplastic hepatocytes by in-situ hybridization. Although TGF-betarII expression was correlated with TGF-beta1 immunoreactivity during early phase of carcinogenesis, hepatocytes in most nodules in 7th, 8th, 9th month and carcinomas showed decreased or little immunoreactivity for TGF-betarII. Based on the above results, it is concluded that TGF-beta1 expression increases not only in precancerous nodules but also in HCCs and its increase seems to be correlated with decrease or loss of TGF-betarII expression although its mechanism remains unclear. Hepatocytes may be a major cellular source of TGF-beta1 during hepatocarcinogenesis.
Carcinogenesis ; Carcinoma, Hepatocellular ; Cytoplasm ; Diethylnitrosamine* ; Female ; Hepatectomy ; Hepatocytes ; Humans ; Liver ; Polymerase Chain Reaction ; Rats, Sprague-Dawley* ; Receptors, Transforming Growth Factor beta* ; RNA, Messenger* ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1* ; Transforming Growth Factors*

OBJECTIVES: Despite the importance of human immunodefi-ciency virus(HIV) transmission through heterosexual contact, the features of heterosexual transmission has not been well studied in Korea. So we conducted a cross sectional study to determine the transmission rates in married couples and assess risk factors for male to female heterosexual transmission of HIV. METHODS: 169 HIV-infected males and their female sex partners were recruited from 1985 to June 1998. We examined female sex partners HIV infection status and interviewed male index partners and their female sex partners about demographic characteristics and sexual practices. We analysed heterosexual transmission rate by epidemiologic characteristics, disease status and sexual practices. And we assessed risk factors for HIV infection by univariate and multivariate analysis. RESULTS: 30 female sex partners were infected at enrollment, yielding an transmission rate of 17.8%. Among couples who had used condoms consistently, none of the female sex partners was infected with HIV. In univariate analysis the significant risk factors were full blown AIDS status (OR=4.1, 95% CI: 1.49-11.43) and low CD4 T cell count of index partners at enrollment (OR=7.8, 95% CI: 2.19-27.80). In multivariate analysis HIV-1 RNA levels was significant risk factor when adjusted by CD4 T cell counts and mean sexual contacts per month (OR=19.2, 95% CI: 1.03-357.59) CONCLUSION: The risk of male to female heterosexual transmission increased with advanced stages of HIV infection in the index male partners.
Cell Count ; Condoms ; Family Characteristics ; Female* ; Heterosexuality* ; HIV Infections ; HIV* ; HIV-1 ; Humans ; Korea* ; Male* ; Multivariate Analysis ; Risk Factors* ; RNA

Clear cell sarcoma of kidney(CCSK) is a rare pediatric neoplasm characterized by a predominating component of clear cells, a predilection for metastases to bone, and a poor prognosis. The incidence of CCSK peaks during the 2nd year of life and adult cases are very rare. We report a case of CCSK encountered in the right kidney of a 39-year-old man. Grossly, it was a lobulated mass showing infiltrative margin, measured 7x5.5x5cm and had a homogeneous gray-tan color with a soft, fish-flesh consistency. Microscopically, about half of the tumor revealed the classic pattern of CCSK, having tumor cell cords or nests separated by the characteristic alveolar capillary networks. The tumor cells had clear pale cytoplasm, bland looking round nuclei and inconspicuous nucleoli. The other half showed the epithelioid-trabecular pattern forming pseudorosette or cord-like structures. Immunohistochemically, there was only a focal positive reaction to vimentin. Ultrastructurally, the tumor cells showed the primitive nephrogenic mesenchymal differentiation such as electron lucent cytoplasm, a small amount of organelles, scanty heterochromatin, inconspicuous nucleoli, and a lack of flocculant basal lamina material around the cytoplasmic membrane. We consider that this is a case of CCSK occuring in the oldest patient ever reported, confirmed by both immunohistochemistry and electron microscopy.
Adult ; Male ; Female ; Humans ; Incidence ; Neoplasm Metastasis

Purpose: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. Materials and Methods: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. Results: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. Conclusion Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

BACKGROUND: Proinflammatory cytokines are one of the causes of diabetes mellitus. However, the exact molecular mechanism by which proinflammatory cytokines induce beta-cell death remains to be clearly elucidated. Glucagon-like peptide-1 (GLP-1) affects the stimulation of insulin secretion and the preservation of beta-cells. Additionally, it may exert an antiapoptotic effect on beta cells; however, the mechanism underlying this effect has yet to be demonstrated. Therefore, we investigated the protective effects of GLP-1 in endoplasmic reticulum (ER)-mediated beta-cell apoptosis using proinflammatory cytokines. METHODS: To induce ER stress, hamster insulin-secreting tumor (HIT)-T15 cells were treated using a mixture of cytokines. Apoptosis was evaluated via MTT assay, Hoechst 33342 staining, and annexin/propidium iodide (PI) flow cytometry. The mRNA and protein expression levels of ER stress-related molecules were determined via PCR and Western blotting, respectively. Nitric oxide was measured with Griess reagent. The levels of inducible nitric oxide synthase (iNOS) mRNA and protein were analyzed via real-time PCR and Western blot, respectively. iNOS protein degradation was evaluated via immunoprecipitation. We pretreated HIT-T15 cells with exendin (Ex)-4 for 1 hour prior to the induction of stress. RESULTS: We determined that Ex-4 exerted a protective effect through nitric oxide and the modulation of ER stress-related molecules (glucose-regulated protein [GRP]78, GRP94, and CCAAT/enhancer-binding protein homologous protein [CHOP]) and that Ex-4 stimulates iNOS protein degradation via the ubiquitination pathway. Additionally, Ex-4 also induced the recovery of insulin2 mRNA expression in beta cells. CONCLUSION: The results of this study indicate that GLP-1 may protect beta cells against apoptosis through the ubiquitination pathway.
Animals ; Apoptosis ; Benzimidazoles ; Blotting, Western ; Cricetinae ; Cytokines ; Diabetes Mellitus ; Endoplasmic Reticulum ; Ethylenediamines ; Flow Cytometry ; Glucagon-Like Peptide 1 ; HSP70 Heat-Shock Proteins ; Immunoprecipitation ; Incretins ; Insulin ; Membrane Proteins ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Polymerase Chain Reaction ; Proteolysis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Sulfanilamides ; Ubiquitin ; Ubiquitination

We report the cytologic features of a case of primary small cell carcinoma of the urinary bladder with high grade transitional cell and signet ring cell carcinomatous components. A 64-year-old male presented with gross hematuria for one week. Computed tomography revealed an ill-defined mass in the left lateral wall of the urinary bladder. Urinary cytology showed hypercellularity with predominantly isolated single cells and clustered cells. They have scanty cytoplasm and naked hyperchromatic nuclei with finely granular nuclear chromatin and rare nucleoli. The tumor cells occurred predominantly singe cells, but a few in clusters. Nuclear molding was prominent. No glandular formation or nesting was noted. The second tumor cells had high nuclear/cytoplasmic ratio, irregular nuclear membrane, and coarse granular chromatin. The background was inflamed and necrotic. The histologic findings of transurethral resection were mainly composed of small cell carcinoma, and partly transitional cell and signet ring cell carcinomatous components. Small cell neuroendocrine carcinoma have distinctive cytologic features to make a proper diagnosis.
Carcinoma, Neuroendocrine* ; Carcinoma, Signet Ring Cell ; Carcinoma, Small Cell ; Carcinoma, Transitional Cell ; Chromatin ; Cytoplasm ; Diagnosis ; Fungi ; Hematuria ; Humans ; Male ; Middle Aged ; Nuclear Envelope ; Urinary Bladder

OBJECTIVE: The purpose of this study was to determine whether quantitative sensory test can be used as a screening test of peripheral polyneuropathy in patients with diabetes mellitus, and to evaluate the severity of peripheral polyneuropathy in patients with diabetes mellitus using quantitative sensory test. METHOD: We performed nerve conduction study to right upper and left lower extremity of the patients. Quantitative sensory test was performed using TSA-2001 thermal sensory analyser on right thenar and left foot dorsum in both diabetic and control groups. RESULTS: 1) The warm sense and heat pain threshold were higher, the cold sense and cold pain threshold were lower in diabetic group than age-matched control group (p<0.05). 2) The warm sense and heat pain threshold were higher, the cold sense and cold pain threshold were lower in diabetic group than young-aged control group (p<0.05). 3) As nerve conduction study results were severe, the cold sense threshold in right thenar were decreased (p<0.05). CONCLUSION: Quantitative sensory study in patients with diabetes mellitus are sensitive to identify neuropathic change; thus, they would be used as the screening method of diabetic peripheral polyneuropathy.
Diabetes Mellitus* ; Foot ; Hot Temperature ; Humans ; Lower Extremity ; Mass Screening ; Neural Conduction ; Pain Threshold ; Polyneuropathies*

Bronchogenic cysts are congenital lesions usually observed in the mediastinum, near the tracheal carina and middle mediastinum. Herein, we present an exceedingly rare case of intradiaphragmatic bronchogenic cyst with an infectious complication in a 52-year-old man. Chest CT and three-dimensional volume rendered reconstructed images revealed an oval, cystic mass with multiple nodular calcifications, centered in the left diaphragm crus. CT facilitated documentation of the healing process of this rare entity, revealing decrease in size and increase in internal density.

Nasopalatine duct cysts are the most common non-odontogenic cysts that occur in the maxilla. Cholesterol granulomas, on the other hand, are commonly found in patients with chronic middle ear disease, but rarely occur in the paranasal sinuses. We report a rare case of a 30-year-old woman who was treated for a nasopalatine duct cyst and cholesterol granuloma at the same time. The patient complained of sudden nasolabial pressure and right nasal obstruction from three weeks ago. A 3 cm sized cystic mass, diagnosed as a nasopalatine duct cyst, was observed in the maxilla and haziness of the right maxillary sinus suspected of chronic rhinosinusitis was detected by computerized tomography. Marsupialization of the nasopalatine duct cyst was performed through the endoscopic transnasal approach. Solid mass in the maxillary sinus, diagnosed with cholesterol granuloma by pathology after surgery, was completely removed by endoscopic sinus surgery. The patient was followed up for 18 months without any recurrence or complications.

Adenoma malignum is a well differentiated form of adenocarcinoma. Despite of benign histologic appearance, this tumor has malignant clinical course. Because of its rarity and subtle histologic changes, it may be missed. Therefore it has poor prognosis. Early diagnosis and early treatment is required by thorough examination. We report one case of adenoma malignum of uterine cervix with a brief review of the literature.
Adenocarcinoma ; Adenoma* ; Cervix Uteri* ; Early Diagnosis ; Female ; Prognosis