Tatsuro Shimokama

Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis

Recent observations have demonstrated the presence of activated T lymphocytes and macrophages in human atherosclerotic lesions. Cells found within these lesions produce cytokines that alter vascular homeostasis in a manner that promotes atherogenesis. To elucidate the role of these immunocompetent cells in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic features of the cellular infiltrates was studied in normal aortas from children; and in later phases of the disease (including fatty streaks and fibrous or atheromatous plaques). Semi-quantitative analysis of cytokine-expressing cells was also investigated with serial sectioning. In 4 of 9 young subjects, the grossly normal aorta contained relatively cell-rich areas which were located preferentially around the ostia of intercostal arteries and were composed of isolated or layered T lymphocytes and macrophages. In these prelesional areas, interleukin-1 (IL-1), IL-2 receptor (IL-2R) and tumour necrosis factor (TNF) were detected in the cytoplasm of the infiltrating cells, whereas no detectable reactivity was noted for IL-2, IL-6, interferon-γ (IFN-γ) or lymphotoxin (LT). In fatty streaks and full-grown atheromas including “cap” and “shoulder” regions, various numbers of T lymphocytes, macrophages and macrophage foam cells were present. In these lesion areas, especially where the cellular infiltrates were numerous, macrophage foam cells and smooth muscle cells expressed not only IL-1 and TNF but also IL-6. The ratio of IL-2R positive cells showed a tendency to decrease with advance of the disease process. Electron-microscopic examination of lesion areas demonstrated ultrastructural aspects of the cognate cellto-cell interaction, as shown by the direct apposition of lymphocytes to macrophages or macrophage foam cells. These results suggest that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherosclerosis.

Increased immunoreactivity of endothelin-1 and endothelin B receptor in human atherosclerotic lesions. A possible role in atherogenesis.

This study was designed to analyze the distribution and localization of endothelin-1 (ET-1) and ET receptors (ET(A) and ET(B)) at different stages of human atherosclerotic lesions by immunohistochemistry. Compared with ET(A) receptors, there was increased immunoreactivity of ET-1 and ET(B) receptor in both unfoamy and foamy macrophages and T lymphocytes in fatty streak and fibrous plaque lesions. In addition, medial SMCs located just beneath the foam cell lesions revealed a higher intensity of ET(B) receptor immunoreactivity than those located beneath the normal-looking intima without foam cells. In fibrous plaques, intimal SMCs near foam cells showed an increased density of ET receptors with predominant ET(B) immunoreactivity. In the areas where SMCs showed ET(B) receptor, ET-1 immunoreactivity was also enhanced. These results suggest that accumulation of foamy macrophages and T lymphocytes may modulate the switching of ET receptor subtypes from ET(A) to ET(B) in vascular SMCs. and that the enhanced ET system mediated by ET(B) receptors may play active roles in the progression of atherosclerosis.

The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: clinicopathological analysis

BackgroundWe evaluated the accuracy and feasibility of real-time elastography for detecting prostate cancer, using prostatectomy specimens.MethodsThis study was based on clinicopathological findings in 51 patients with prostate cancer who were referred for elastography at the time of prostate biopsy. We compared transverse pathology sections with elastographic moving images (EMIs) to determine the detection rate of cancer, the relationship between tumor location and the elastographic findings, and the relationship between the Gleason score and the elastographic findings.ResultsIn 15 patients (29%), all EMIs were in complete agreement with tumor location (category I), in 28 patients (55%), the EMIs agreed with tumor location, but showed some disagreement (category II), and in 8 patients (16%) there was disagreement of the elastographic findings with tumor location or the tumors were undetectable by elastography (category III). However, in category III, all tumors were detected as low-echoic by B-mode ultrasonography. We divided the prostate into three different regions (anterior, middle, and posterior), and found that 30/32 (94%) anterior tumors, 13/17 (76%) middle tumors, and 16/28 (57%) posterior tumors were detected by elastography. The proportions of cancers detected by elastography (categories I+II/total) was 100% in the patients with a Gleason score of 6, 85% in those with a score of 7 or 8, and 63% in those with a score of 9 or 10.ConclusionReal-time elastography in conjunction with B-mode ultrasonography significantly improves the detection of prostate cancer. One of the characteristic findings of elastography is its excellent detection of anterior tumors. The low detection rate of high-grade tumors in this analysis was likely due to the predominance of high-grade tumors in a peripheral location compared to the anterior location of the low-grade tumors.

Real-time Elastography for the Diagnosis of Prostate Cancer: Evaluation of Elastographic Moving Images

OBJECTIVEnElastography is a technique for detecting the stiffness of tissues. We applied elastography for the diagnosis of prostate cancer and evaluated the usefulness of elastography for prostate biopsy.nnnMETHODSnThe subjects of this study were 311 patients who underwent elastography during prostate needle biopsy at Hitachi General Hospital. Strain images obtained during compression of the prostate tissue were displayed on a monitor and recorded on the computer. The elastographic moving images (EMI) were evaluated retrospectively. The evaluable images and biopsy results were compared in terms of the feasibility and accuracy.nnnRESULTSnThe median patient age was 67 years (range 50-85 years), the median serum level of prostate-specific antigen was 8.4 ng/ml (range 0.3-82.5 ng/ml) and the median prostate volume was 42.6 ml (range 12-150 ml). Among the 311 patients, prostate cancer was detected in 95 patients (30%) by biopsy. The diagnostic sensitivity was 37.9% for digital rectal examination (DRE) and 59.0% for transrectal ultrasonography (TRUS), whereas it was 72.6% for elastography and 89.5% for the combination of TRUS and elastography. Elastography-positive EMIs with negative biopsies were eventually determined to be due to benign prostatic hyperplasia.nnnCONCLUSIONnElastography has a significantly higher sensitivity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

Inflammatory and immunological nature of atherosclerosis

Recent studies have revealed that atherosclerosis bears several similarities to chronic inflammation. One of the earliest events in both human and experimental atherosclerosis is adhesion of monocytes and T lymphocytes to endothelial surface followed by their migration into the intima. This intimal recruitment of blood derived cells, coupled with the enhanced endothelial permeability to plasma proteins, indicates a potential role for inflammatory mechanisms in early atherogenesis. Colocalization of T lymphocytes and macrophages in all stages of human atherosclerosis, from grossly normal prelesional intima to fully advanced atheromatous plaques, and expression of cytokines and MHC class II antigens by many types of cells of the lesion provide further evidence that atherosclerosis has both the inflammatory and immune nature. The presence of T lymphocytes and macrophages in pairs with a close contact to each other suggests that cognate cell to cell interaction also plays a pivotal role in the pathogenesis of atherosclerosis. It seems conceivable that the T lymphocyte-macrophage interaction particularly takes place in the areas where atherosclerotic lesions are in progress or being active. The pathogenic potentials of immunologic factors are fruitful subjects for further investigation.

Clear cell odontogenic carcinoma. A case report with massive invasion of neighboring organs and lymph node metastasis.

Clear cell odontogenic carcinoma is a rare and unusual tumor that occurs in the jaws. This tumor is generally considered to be of a low grade of malignancy. We describe a patient with a huge clear cell odontogenic carcinoma that originated in the mandible and exhibited massive invasion into the adjacent tissues and metastases to the submandibular lymph nodes. The ultrastructural and immunohistochemical details are described.

Real-Time Balloon Inflation Elastography for Prostate Cancer Detection and Initial Evaluation of Clinicopathologic Analysis

OBJECTIVEnThe use of elastography is limited for prostate cancer detection because of the difficulty in obtaining stable and reproducible images. To overcome these limitations, we developed a new technique called real-time balloon inflation elastography (RBIE); with RBIE, balloon inflation and deflation are used in place of manual compression. We present the accuracy and feasibility of the RBIE technique for detecting prostate cancer.nnnMATERIALS AND METHODSnThe results of a pathologic analysis of 55 prostatectomy specimens were compared with elastographic moving images obtained at the time of biopsy of the prostate.nnnRESULTSnThe RBIE technique generated stable and repeatable elastographic moving images. The percentage of images affected by artifact due to slippage in the compression plane was reduced to 1% using the RBIE method compared with 32% using the manual compression method. With regard to tumor location, elastographic moving images obtained using the RBIE technique were in complete agreement with clinicopathologic evaluation of tumor location in eight cases (15%), showed partial agreement in 43 cases (78%), and disagreed in four cases (7%). In three different regions of the prostate, 84% of anterior tumors, 85% of middle tumors, and 60% of posterior tumors were detected. The tumor detection rates by Gleason score were 60% in tumors with a Gleason score of 5 or 6, 73% in tumors with a Gleason score of 7, 72% in tumors with a Gleason score of 8, and 74% in tumors with a Gleason score of 9 or 10.nnnCONCLUSIONnThe RBIE method improved the quality of elastographic moving images compared with the manual compression method. High-grade tumors and tumors of impalpable regions of the prostate were more frequently detected using RBIE. We conclude that RBIE is a promising method with which to detect prostate cancer.

Renal amyloidosis. Correlations between morphology, chemical types of amyloid protein and clinical features.

Sixty-one autopsy cases of renal amyloidosis were reviewed to assess the relationship of renal pathology to chemical types of amyloid and clinical features. Glomerular amyloid deposition was divided on the basis of morphological characteristics, into four types: a mesangial nodular type showing nodular mesangial deposits with sparse capillary wall involvement (25 cases), a mesangio-capillary type disclosing diffuse amyloid deposition in the mesangium and along both sides of the glomerular basement membrane (19 cases), a perimembranous type principally involving the subepithelial side of the basement membrane invariably characterized by exuberant spicular arrangement (6 cases), and a hilar type showing amyloid deposits almost exclusively in hilar arterioles (11 cases). Twenty-four of 25 cases of mesangial nodular type (96%) showed amyloid protein of AA type. However, mesangio-capillary and perimembranous types were associated with deposition of AL amyloid protein in 15 of 19 (79%) and all 6 cases, respectively. Nephrotic syndrome was more frequent in patients with AL amyloidosis; notably, all patients with perimembranous type had nephrotic syndrome irrespective of the extent of glomerular amyloid deposits. Chronic renal failure and renal death appeared more common in mesangial nodular type in which the extent of glomerular amyloidosis correlated with that of vascular amyloid deposits. The results obtained suggest that the chemical type of glomerular amyloid protein (AA vs AL) is associated with significant differences in the morphological, clinical and prognostic features of the renal involvement.

Atherosclerosis and Macrophages

Atherosclerosis is undoubtedly a disease of many facets and in this review we have merely touched one angle of this issue. The best‐established cause of the disease is hyper‐cholesterolemia. Since the important role of macrophages in lipoprotein metabolism has been confirmed, current interest is focused on the role of macrophages in atherosclerosis. The origin and tissue distribution of foam cells have been discussed in detail, because they are the principal cells in the earliest lesions, the so‐called fatty streaks. Once thought to be derived exclusively from smooth muscle cells, foam cells are now known to originate largely from monocytes that enter the intima and become transformed into macrophages. Exactly how monocytes are recruited and retained in the artery wall is not fully understood, but it is certain that the initial event involves adhesion to the endothelial surface followed by penetration under the influence of a chemotactic factor(s). Hypercholesterolemia contributes much to this phenomenon by affecting both monocyte macrophages and endothelial cells. Intensive current research is increasing our understanding of the dynamic interaction between macrophages and both lipoproteins and vascular cells, and its immediate relevance to lesion formation. Closer scrutiny of the biology and molecular mechanism of the process of atherosclerosis may ultimately permit intervention in and slowing of the progress of this catastrophic human disease using new modalities. Acta Pathol. Jpn. 39: 473∼486, 1989.

Leiomyoma exhibiting a marked granular change : granular cell leiomyoma versus granular cell Schwannoma

Granular change of leiomyoma or granular cell leiomyoma is rare and not well recognized. It may be confused with the common variety of granular cell tumor, which is currently regarded as being of schwannian origin. A case of granular cell leiomyoma in the periurethral region of a 40-year-old woman is reported. Microscopy indicated that the tumor consisted of polygonal or fusiform cells with coarse, granular eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for desmin and actin, but negative for neuron-specific enolase and S-100 protein. Electron microscopy revealed myofilaments in the tumor cells, thus documenting the myogenic origin of the granular cells. The granules were ultrastructurally similar to those of granular cell schwannoma as described in the literature. It is likely that granular cell tumor arises from different tissues.