Semi-quantitative HPV viral load in patients with ASC-US cytology: viral load correlates strongly with the presence of CIN but only weakly with its severity.

OBJECTIVES: This study was performed to evaluate the prognostic significance of human papillomavirus (HPV) viral load, expressed in relative light units (RLUs), in patients with atypical squamous cells of undetermined significance (ASC-US) cytology. METHODS: A total of 349 ASC-US cases with HPV infection, detected using Hybrid Capture 2, were diagnosed histologically. A colposcopically directed punch biopsy was performed on acetowhite areas. Endocervical curettage biopsy and random cervical punch biopsy in four quadrants were performed in unsatisfactory colposcopy cases. In negative colposcopy cases, random cervical punch biopsy in four quadrants was performed. RESULTS: Case with no cervical intraepithelial neoplasia (CIN), CIN1 and CIN2+ (CIN2/CIN3) accounted for 162, 135 and 52 cases, respectively. The mean age showed no difference among the three groups (P = 0.510). There was a significant correlation between RLU values and the presence of CIN (P < 0.001), but less so with its severity: the median RLU values for negative, CIN1 and CIN2+ cases were 42.68, 146.45 and 156.43, respectively, with widely overlapping confidence intervals. The cut-off values of RLU to detect CIN1+ and CIN2+ were 6.73 and 45.64, respectively. CONCLUSIONS: The HPV viral load in ASC-US cases showed a significant correlation with the presence of CIN and less so with its severity, and showed large overlap of viral loads between grades of CIN. In ASC-US cases, RLU was not an accurate predictor of immediate high-grade CIN.

ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction.

OBJECTIVES: Angiotensin-converting enzyme (ACE) polymorphism may play a role in stroke and silent brain infarction (SBI) susceptibility, but the results among the populations studied to date have not been consistent. Thus, we investigated the association between ACE genotypes and ischemic stroke and SBI in Korean patients. SUBJECTS AND METHODS: DNA samples from 237 stroke patients, 264 SBI patients and 234 age-matched controls were amplified using polymerase chain reaction to detect the ACE ins/del (I/D) polymorphism. Genotype was determined by the presence of a 490-bp band (I allele) or a 190-bp band (D allele) in agarose gel electrophoresis. RESULTS: Odds ratios of the I/D and D/D genotypes and the overall (I/D + D/D) for the I/I genotype were significantly different between stroke patients and normal controls. However, there was no significant difference between patients with SBI and controls. CONCLUSIONS: This study is the first report of a significant association between ACE polymorphism and ischemic stroke in the Asian population. Although no consistent associations have been found between ACE polymorphism and stroke in the populations studied to date, the ACE polymorphism may be a genetic determinant of ischemic stroke, at least in Korean patients.

Differential expression of manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase in gastric adenocarcinoma and normal gastric mucosa.

AIMS: The biologic significance of antioxidant enzymes (AOEs) in gastric adenocarcinoma is still unclear. The aims of this study was to investigate the differential expression of AOEs in gastric carcinoma cells and non-cancerous counterparts and the relationship with the various clinicopathologic variables in gastric cancer patients. METHODS: Expression status of MnSOD, Cu/ZnSOD, and catalase was evaluated immunohistochemically in 120 paired gastric cancer and adjacent non-cancerous tissue. The tissues were fixed in absolute methanol immediately after surgical resection and immunohistochemistry was performed by microprobe system using tissuemicroarray slides. RESULTS: All AOEs revealed moderate to strong immunoreactivity in the parietal and intestinal metaplastic cells. Stromal cells in both cancer and non-cancerous tissue expressed MnSOD and catalase but Cu/ZnSOD. Immunoreactivity of MnSOD and catalase was increased in gastric carcinoma cells compared to their non-cancerous counterparts and revealed an association with intestinal type adenocarcinomas whereas immunoreactivity of Cu/ZnSOD did not reveal significant difference between cancer and non-cancerous mucosal cells. CONCLUSIONS: Expression of MnSOD, Cu/ZnSOD, catalas in gastric cancer cells and non-cancerous counterparts was different and increased MnSOD and possibly catalase may in part be responsible for the increased risk of intestinal type adenocarcinoma of the stomach.

Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography.

Optical coherence tomography angiography (OCTA) is a noninvasive method of 3D imaging of the retinal and choroidal circulations. However, vascular depth discrimination is limited by superficial vessels projecting flow signal artifact onto deeper layers. The projection-resolved (PR) OCTA algorithm improves depth resolution by removing projection artifact while retaining in-situ flow signal from real blood vessels in deeper layers. This novel technology allowed us to study the normal retinal vasculature in vivo with better depth resolution than previously possible. Our investigation in normal human volunteers revealed the presence of 2 to 4 distinct vascular plexuses in the retina, depending on location relative to the optic disc and fovea. The vascular pattern in these retinal plexuses and interconnecting layers are consistent with previous histologic studies. Based on these data, we propose an improved system of nomenclature and segmentation boundaries for detailed 3-dimensional retinal vascular anatomy by OCTA. This could serve as a basis for future investigation of both normal retinal anatomy, as well as vascular malformations, nonperfusion, and neovascularization.

Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

Thymocytes positively select thymocytes in human system.

We previously demonstrated the expression of MHC class II molecules in a significant percentage of human fetal and postnatal thymocytes. These results, at that time, raised the question as to whether the MHC class II molecules on immature thymocytes could actively be involved in the selection of immature T cells. We have developed a human reaggregate culture system to address this issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have been shown to be a major selecting cell type of positive selection, we were clearly able to see the involvement of MHC class II+ thymocytes during selection process through T-T interaction. In addition, maturation to single positive (SP) cells occurred only in the presence of MHC class II molecules and immature thymocytes were found to be arrested at the double positive (DP) stage of differentiation by blocking of TCR recognition of MHC class II molecules. All these results strongly suggest that human MHC class II+ thymocytes actively participate in the selection of the TCR repertoire, for which TCR recognition of peptide/MHC class II may be an initial determining step.

Immunological classification of T-cell acute lymphoblastic leukaemia using monoclonal antibodies.

We had been able to classify 70 cases of acute lymphoblastic leukemia (ALL) into different immunological subtypes based on surface marker analysis with the aid of a panel of monoclonal antibodies. The relative proportions of different ALL subclasses appears to be similar to those reported from Europe and the U.S.A. Our results also indicated that monoclonal antibodies OKT11, UCHT-2 and WT1 were very useful in defining pre-T or early T subtypes of ALL. The latter leukaemias lack most maturation-linked T-cell markers but share with the other T-ALL the characteristic of low density or undetectable insulin receptors.

Optimal primer selection for clonality assessment by polymerase chain reaction analysis. III. Intermediate and high-grade B-cell neoplasms.

Previous studies have reported that low-grade B-cell lymphoproliferative disorders have variable B-cell monoclonality detection rates by polymerase chain reaction (PCR) analysis. For instance, monoclonal B-cell populations from chronic lymphocytic leukemia/small lymphocytic leukemia and mantle cell lymphoma are most often readily amplified with a single primer pair, whereas follicular lymphomas and plasma cell neoplasms require alternative strategies to approach these higher diagnostic sensitivity standards. Because most published reports have not focused on the variation in PCR B-cell monoclonality detection among subtypes of intermediate and high-grade B-cell neoplasms, additional information is necessary to determine primer selection strategies and identify problematic tumor subtypes within this group. The current investigation, the third part in a series, was aimed at documenting the efficiency of B-cell monoclonality detection by PCR in 71 aggressive B-cell neoplasms of various types using a comprehensive approach. A predetermined panel of primer sets was used in an algorithmic fashion. Specifically, all samples were analyzed with the standard VH-FRIII/JH assay previously shown to have the highest efficiency of monoclonality detection within low-grade B-cell lymphoproliferative disorders. Negative samples were further evaluated with primer sets in the following order until a positive result was observed, or all primer sets were used: (1) bcl-2/JH, (2) VH-FRI family specific/JH, and (3) VH-FRI consensus/JH. Forty-three (61%) of the 71 B-cell neoplasms evaluated with VH-FRIII/JH showed monoclonal B-cell populations. Sequential use of the three reserve primer sets in samples negative with this initial primer pair resulted in an overall improvement in PCR detection from 61% to 82% (58 of 71 specimens) (P < .001). The VH-FRI family specific assay identified B-cell monoclonality in 11 (73%) of these 15 specimens and was the most productive reserve primer set. Individual categories exhibited the following initial (I) and final (F) PCR detection rates: acute lymphoblastic leukemia/lymphoblastic lymphoma, 11 specimens (I = 91% to F = 91%); small noncleaved cell lymphoma, 14 specimens (I = 79% to F = 86% [P > .25]); diffuse large cell lymphoma, 33 specimens (I = 52% to F= 85% [P < .005]) and large cell, immunoblastic lymphoma, 13 specimens (I = 38% to F = 62% [P < .01]). The authors have shown that comprehensive PCR analysis is capable of detecting B-cell monoclonality in a significant proportion of samples from each subtype of intermediate and high-grade B-cell neoplasm. The VH-FRIII/JH assay was an adequate initial primer set, but required augmentation with the reserve PCR assays to attenuate the false negative rate and improve diagnostic sensitivity. The B-cell clonality PCR assay is optimally used as a screening tool and when used in this fashion, the more laborious and time-consuming restriction fragment-Southern blot hybridization (RF-SBH) method for IgH gene rearrangement detection may be limited to a relatively small proportion of PCR-negative aggressive B-cell neoplasms.

Biliary lymphoepithelioma-like carcinoma not associated with Epstein-Barr virus.

We report the case of a 64-year-old man who presented with a hepatic mass and macronodular cirrhosis. The pathologic findings revealed a lymphoepithelioma-like carcinoma arising in the hepatobiliary tract that was morphologically identical to nasopharyngeal undifferentiated carcinoma. However, this tumor was not associated with Epstein-Barr virus infection in molecular studies. Macronodular cirrhosis associated with hepatitis C virus was present in the background liver.

Higher incidence of p53 mutation in cervical carcinomas with intermediate-risk HPV infection.

OBJECTIVE: Inactivation of p53, either through mutation or interaction with human papillomavirus (HPV) E6 oncoprotein, is a characteristic feature of cervical carcinoma cell lines that have been previously studied. To elucidate the role of p53 in the carcinogenesis of Korean cervical carcinomas, 27 HPV-positive and 13 HPV-negative cervical carcinomas were studied in order to evaluate the status of the p53 gene. STUDY DESIGN: The HPV status was ascertained by polymerase chain reaction (PCR) amplification using consensus primers designed from the E6 and E7 open reading frames (ORFs). The p53 mutation status was analyzed by direct sequencing of the PCR product in highly conserved exons 5-8. RESULTS: There was no significant difference in the frequency of the p53 mutation between the HPV-positive and negative cases. All three mutations in the HPV-positive cases were associated with intermediate-risk viruses. The average age of the patients with the p53 mutation was 14 years older than that of patients without the p53 mutation. CONCLUSION: p53 mutations are higher in the so called intermediate-risk HPV positive than HPV 16 or 18 positive cervical carcinomas.

Hepatocellular carcinoma with lung metastasis in a 9-year-old-boy.

Hepatocellular carcinoma (HCC) remains chemoresistant and, therefore, the principal treatment of HCC is surgical resection. After a 9-year-old boy with huge HCC with lung metastasis received the 5 cycles of chemotherapy (cisplatin and Adriamycin), the lung metastasis had been resolved completely and the size of HCC in liver had decreased. Right hepatic trisegmentectomy was performed, and then the additional 3 cycles of chemotherapy was given. Currently, the patient shows no recurrence of HCC 42 months after surgical extirpation.

Comprehensive histologic analysis of interstitial lipolysis with the 1444 nm wavelength during a 3-month follow-up.

A number of near-infrared wavelengths have been proposed and studied for laser lipolysis, but the histologic evaluation of tissue response to laser lipolysis during long-term follow-up has been lacking. A 1444 nm Nd:YAG laser with better absorption in both fat and water has recently attracted attention. The present study was designed to investigate the comprehensive histopathology of 1444 nm Nd:YAG laser-assisted lipolysis at different energy levels during a 3-month follow-up. Laser lipolysis was performed on porcine fat tissue in vivo using a 1444 nm Nd:YAG laser (AccuSculpt®, Lutronic Corporation, Ilsan, Republic of Korea) and the total energies delivered interstitially to 10x10 cm² areas were 750 J, 1500 J, 2250 J, 3000 J, 3750 J, 4500 J, and 5250 J. Biopsy samples were taken and histologically analyzed immediately after biopsy and at 1, 2, 4, and 12 weeks postoperatively. With a fluence setting above 3000J/100 cm², inflammation was severe and remained by the 3-month follow-up, resulting in severe scarring of the fat tissue. Below this energy level, mild lobular inflammation in the early phase biopsy had resolved with no scarring by the 3-month follow-up. No histologic changes in the epidermis or dermal connective tissue were present. This study suggested that controlling the energy level is important for clinical applications of laser lipolysis with no significant complications.

Histopathologic study of the so called 'palpation thyroiditis'.

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis.

Syringomatous adenoma of nipple--a case report.

A syringomatous adenoma of the nipple is a benign locally infiltrating neoplasm histologically similar to the syringoma of the skin. Morphologically similar lesions have been described as adenoma of the nipple or florid papillomatosis. Patient was a 33 year old woman who was admitted with a history of bloody nipple discharge from her right breast. With a clinical impression of Paget's disease explorative mastectomy was performed. Microscopically typical tubular and duct like structures with syringomatoid features were present throughout the stroma of the nipple.

The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma--a multivariate analysis of prognostic factors.

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Metastatic renal cell carcinoma in a meningioma: a case report.

Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.