Fumiaki Tezuka

Elasticity Imaging of Atheroma With Transcutaneous Ultrasound Preliminary Study

Background Knowledge of the physical properties of atherosclerotic plaque is essential when evaluating its vulnerability in a clinical setting. Such knowledge, however, is still difficult to obtain with the various approaches developed to date. Methods and Results This article describes a noninvasive method for evaluating the regional elasticity (the elastic modulus in the circumferential direction) of tissue surrounding atherosclerotic plaque in which a novel phased tracking method is applied to measure minute changes in thickness of each of the multiple layers of the arterial wall during one heartbeat. By comparing the pathological findings with the distribution of elasticity, average elasticity of lipid and that of a mixture of smooth muscle and collagen fiber can be determined. On the basis of these reference parameters, each point is statistically categorized as lipid, mixture, or other. Thus, the plaque is electronically stained using transcutaneous ultrasound. By applying the method to the common carotid arteries, the presence of thin collagen fiber was clarified along the arterial axis for normal subjects, whereas soft inclusion of lipid was found for every plaque in subjects with hyperlipidemia. Conclusion This novel method offers potential as a diagnostic technique for detection of plaque vulnerability with high spatial resolution. (Circulation. 2003;107:3018‐3021.)

Urocortin expression in the human central nervous system

Urocortin is a recently identified neuropeptide of the corticotrophin‐releasing factor (CRF) family in the mammalian brain and has been demonstrated to stimulate ACTH secretion from pituitary cells, but its expression in human brain tissue including the hypothalamus has not been examined. In this study, we first examined urocortin expression in the hypothalamus (20 cases) and pituitary stalks (17 cases) of human brain obtained from autopsy using immunohistochemistry and mRNA in situ hybridization.

THE AH RECEPTOR IS NOT INVOLVED IN 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-MEDIATED APOPTOSIS IN HUMAN LEUKEMIC T CELL LINES

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental pollutant causing public concern. Its toxic effects include disruption of the immune, endocrine, and reproductive systems, impairment of fetal development, carcinogenicity, and lethality in rodents. Here, we report that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines. This cell death was found not to be dependent on an aryl hydrocarbon receptor and to be inhibited by the inhibitor of tyrosine kinases and caspases. Apoptosis-linked c-Jun N-terminal kinase is rapidly activated in these cells by the treatment with TCDD. A dominant-negative mutant of c-Jun N-terminal kinase prevented cell death in the treatment with TCDD. Furthermore, TCDD decreases the Bcl-2 protein level in these cell lines. These findings will help in the understanding of the molecular mechanism underlying TCDD-mediated immunotoxicity.

Atypical adenomatous hyperplasia and adenocarcinoma of the human lung: Their heterology in form and analogy in immunohistochemical characteristics

In a previous study, morphometry and multivariate cluster analysis was performed on 97 lesions. These consisted of atypical adenomatous hyperplasia (AAH), considered to be an important lesion corresponding to a step of carcinogenesis for adenocarcinoma of the human lung, Clara cell type, and type 2 pneumocyte type adenocarcinomas. Although AAH and the two types of adenocarcinoma were re‐classified into three clusters and AAH was defined in clear morphologic terms, the biologic nature of AAH has yet to be clarified. In the present study, immunohistochemical analysis was performed to gain a deeper understanding of the relationship between AAH and the two types of adenocarcinoma, and to compare the results with those obtained by morphometry.

Origin and extension of intraductal papillomas of the breast: A three-dimensional reconstruction study

SummarySurgical specimens from fifteen patients with intraductal papilloma were reconstructed three-dimensionally from semi-serial sections to visualize the intraductal distribution of papillomas. Our results showed two basically different papillomas. In five patients, the papillomas were single and originated in the large ducts such as the segmental or subsegmental duct, but did not involve the terminal ductal-lobular units (TDLU); this type corresponded to the so-called solitary papilloma. In the remaining ten specimens, the papillomas were multifocal three-dimensionally; each had a root in the TDLU and spread into the large ducts, suggesting its purely peripheral origin. In view of this striking difference, and of possible canceration of ductal peripheries, a nomenclature of peripheral vs central papillomas is proposed instead of the conventional multiple vs solitary. Duct papillomatosis, invariably situated within the TDLU, was shown to be a continuation of peripheral papilloma and was regarded accordingly as a prepapillomatous condition.

Prevalence of drug-resistance-associated mutations in antiretroviral drug-naive Zambians infected with subtype C HIV-1.

The ability of HIV-1 to evolve resistance to antiretroviral drugs leads to treatment failure. By nucleotide sequencing of HIV-1 subtype B isolates, amino acids responsible for drug resistance have been identified. Less information is available, however, on the extent and distribution of these amino acids in HIV-1 nonsubtype B viruses circulating mainly in developing countries. More HIV-infected patients in the developing world are now using antiretroviral drugs, and hence there is a need to monitor drug resistance mutations in HIV-1 non-subtype B viruses. This study examines the prevalence of drug resistance mutations in 28 antiretroviral drug-naive HIV-1-infected Zambians. HIV-1 proviral DNA was extracted from peripheral blood mononuclear cells. The region encompassing gag p17 to env C2-V3-C3 was amplified by the polymerase chain reaction followed by direct sequencing. Sequence analyses for drug resistance-associated mutations in th e protease and reverse transcriptase genes, and HIV-1 subtyping, were done. Overall, 92.8% of the generated sequences were HIV-1 subtype C. The generated sequences revealed only secondary associated, but no primary, drug-resistance mutations The most frequent secondary mutations in the protease and RT genes were, respectively, I93L(91.7%), L89M (79.2%), M3611V (79%, 4.2%), and R211K (70.8%), S48T (62.5%). The atypical residues M41N (3.6%) and D67A (3.6%) were detected in the RT gene. This study reveals many naturally occurring polymorphisms in HIV-1 subtype C isolates from antiretroviral drug-naive individuals. Such polymorphisms could lead to rapid treatment failure and development of drug-resistant HIV-1 mutants in individuals undergoing antiretroviral therapy.

Diagnostic Efficacy and Validity of the ThinPrep Method in Cervical Cytology

OBJECTIVE To examine the efficacy of the ThinPrep method, an automated, fluid-based technique for the collection and preparation of exfoliated and aspirated cells in cervical cytology. STUDY DESIGN A total of 251 patients participated. From each patient a sample was obtained by scraping with a wooden spatula, split and prepared with both conventional Papanicolaou and ThinPrep methods. In the ThinPrep processor, epithelial cells were homogenized in a vial of preservative solution and randomly sampled onto a microscopic slide. From a single vial of sample suspension a series of 10 ThinPrep slides of the same quality were made. All cells were concentrated within an approximately 20-mm-diameter circle in a uniform, thin layer on the ThinPrep slide. RESULTS Twenty-five percent of the screening area, 10% of the epithelial cells observed and 50% of the screening time were required to arrive at a final diagnosis as compared with the Papanicolaou smear. Virtually complete concurrence was ascertained between the Papanicolaou and ThinPrep diagnoses, for direct agreement of 95.3% and agreement within one diagnostic grade of 99.5%. CONCLUSION An overall improvement was ascertained in the preparation of microscopic slides and the recognition of abnormal cells with the ThinPrep method.

Immunophenotypic analysis of extranodal non-Hodgkin's lymphomas in the oral cavity.

Fifty cases of extranodal non-Hodgkins lymphoma arising in the oral cavity were reclassified using the updated Kiel classification. In order to determine the antigenic phenotype of the proliferating cells in oral lymphoma, we used a panel of paraffin effective antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. The median age of the patients was 53 years, with a male predominance (M:F = 1.9: 1). The great majority of oral non-Hodgkins lymphomas were B-cell lymphomas. There were 12 low-grade B-cell lymphomas (comprising one mucosa-associated lymphoid tissue, four centrocytic and seven centroblastic-centrocytic lymphomas) and 25 high-grade tumors (comprising 17 centroblastic, two immunoblastic, two Burkitts and four lymphoblastic lymphomas). All 37 B-cell malignancies showed reactivity for L 26 and KiB 3. A monotypic immunoglobulin staining pattern, as revealed by light chain restriction, was found in 21 cases (57%) of the non-Hodgkins lymphomas confirming their B-cell origin. Furthermore, monotypic staining for kappa-chain predominated (16/21 kappa, 5/21 lambda). Only a small number (6 cases) was of T-cell lineage and all cases showed positive reaction for UCHL 1, MT 1 and DFT 1. In one of six T-cell lymphomas, Ber-H 2 positive anaplastic large cell lymphoma was detected. Such a case was documented for the first time in the primary extranodal non-Hodgkins lymphoma of the oral cavity. Five cases could be assigned with certainty to the histiocytic system. These cases were positive for cathepsin D and KP 1 LN 3, which recognized Ia (HLA-DR) antigens, was demonstrated most frequently in high-grade B-cell lymphomas, T-cell lymphomas and true histiocytic lymphomas.

Carcinoma ex pleomorphic adenoma of the palatal minor salivary gland with extension into the nasopharynx

Carcinoma ex pleomorphic adenoma presenting in the nasopharynx is extremely rare. We present a case of carcinoma ex pleomorphic adenoma occupying the nasopharynx and the soft palate in a 51-year-old woman. To the best of our knowledge, this is the first reported case of carcinoma ex pleomorphic adenoma in the nasopharynx.

Coexistence of Pemphigus vulgaris and herpes simplex virus infection in oral mucosa diagnosed by cytology, immunohistochemistry, and polymerase chain reaction

A case of Pemphigus vulgaris concurrent with herpes simplex virus (HSV) infection in a 53‐yr‐old female is described, in which the diagnosis was based on oral scraping cytology. Two populations of abnormal cells were identified in the oral smear. One abnormal cell population was characterized by the presence of numerous single cells and sheets and smaller aggregates of loosely cohesive epithelial cells that appeared to have only a few points of intercellular attachment. A second population of abnormal cells showed characteristic signs of HSV infections such as ground‐glass nuclear appearance and multinucleation. Subsequently, diagnosis of HSV infections based on polymerase chain reaction was applied to identify the specific DNA for HSV type 1 in the Papanicolaou specimens. To our knowledge, this is the first case in which the coexistence of Pemphigus vulgaris and HSV infection in the oral mucosa was established by cytologic diagnosis. This is discussed in view of our recent experience with this unusual oral lesion. Diagn. Cytopathol. 1998;19:446–450.