Tadaaki Yokota

Evidence That Implicates the Parathyroid Hormone–Related Peptide in Vascular Stenosis Increased Gene Expression in the Intima of Injured Rat Carotid Arteries and Human Restenotic Coronary Lesions

Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic (407 +/- 53 cells/mm2; range, 143 to 739) than in stable angina (50 +/- 12 cells/mm2; range, 18 to 132; P<.05) or unstable angina (129 +/- 16 cells/mm2; range, 21 to 232; P<.05) specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation.

Etiological factors in primary hepatic B-cell lymphoma

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren’s syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells.

Cardiac papillary fibroelastomas: Rationale for excision

We experienced a case of papillary fibroelastoma of the left ventricular outflow tract in a patient with severe valvular heart disease that was detected only by transesophageal echocardiography. Preoperative detection of this lesion altered the surgical procedure to include resection of the mass through the aortic valve annulus along with repair/replacement of the valves. The literature documents sufficient morbidity/mortality to support excision of these lesions regardless of symptoms or location.

Severe chronic active Epstein-Barr virus infection accompanied by virus-associated hemophagocytic syndrome, cerebellar ataxia and encephalitis

We present a rare case of chronic active giftein‐Barr virus (EBV) infection showing various clinical outcomes. A 26‐year‐old man was admitted to our hospital due to persistent fever and dyspnea. Serologic response of the patient to EBV indicated chronic active infection. He showed pleuritis, parotitis, chronic hepatic dysfunction, disseminated intravascular coagulation, virus associated hemophaghocytic syndrome, acute rhabdomyolysis, acute renal failure, acute cerebellar ataxia, encephalitis and multiple brain abscesses. None of acyclovir, gancyclovir, prednisolone or interleukin‐2 was effectual to abolish those abnormalities. This is the first report of transient cerebellar ataxia which aggravated to panencephalitis associated with chronic EBV infection.

Pathologic aspects of polytetrafluoroethylene sutures in human heart

BACKGROUND Polytetrafluoroethylene (PTFE) sutures have been widely used as a mitral chord substitute. We present the cases of 4 patients who underwent mitral valve repair with chordal replacement by PTFE sutures and these required another operation. This gave us the chance to examine the PTFE sutures. METHODS Structural analysis of the PTFE sutures was performed 26 to 378 days postoperatively. The specimens were examined grossly, microscopically, and by scanning or transmission electron microscopy or both. RESULTS The PTFE suture in 1 patient was found to be completely covered with endothelial cells 154 days postoperatively. There was no calcification, and the flexibility and pliability of the PTFE sutures was preserved. Even though the PTFE sutures seemed uncovered on visual inspection, there was a thin lining of collagen and fibrin on the surface. Endothelial cells were seen in areas that looked clear in one specimen 26 days postoperatively. CONCLUSIONS We think that the new layer of collagen could be promising in terms of durability and that the endothelial layer wil resemble normal tissue in its anticoagulant properties.

Localized amyloidosis in squamous cell carcinoma of uterine cervix: Electron microscopic features of nodular and star-like amyloid deposits

An ultrastructural study of amyloid deposits in four cases of squamous cell carcinoma of uterine cervix was performed. The amyloid deposits reacted with anti-keratin antiserum on frozen sections. Amyloid deposits showed nodular (4 cases) and star-like forms (3 cases). Nodular amyloid deposits were composed of slightly whorled fibrils, measuring 7–10 nm in width. Some of them contained cellular debris and thicker, more electron-dense filaments than amyloid fibrils. In three cases, filamentous tumour cells and filamentous masses were observed together with amyloid. Star-like amyloid deposits were composed of bundles of straight amyloid fibrils. Some of the tumour cells in contact with star-like amyloid deposits had deep cytoplasmic invaginations, where closely packed amyloid fibrils were arrayed in parallel fasion. In addition, a few tumour cells had membrane-bound amyloid fibrils in the cytoplasm. It is suggested that nodular amyloid deposits are derived from the tumour cells through filamentous degeneration. Amyloid fibrils in star-like amyloid deposits are thought to be formed within the cytoplasm or in the vicinity of invaginated cytoplasmic membranes of the tumour cells.

Fibro-fatty volume of culprit lesions in Virtual Histology intravascular ultrasound is associated with the amount of debris during carotid artery stenting.

Objectives: This study aimed to evaluate the relationship between the amount of aspirated debris during distal balloon-protected carotid artery stenting (CAS) and the pre-intervention plaque composition, as assessed by Virtual Histology™ (VH) intravascular ultrasound (IVUS). Methods: The study subjects were 25 consecutive patients (mean age, 73.0 ± 5.2 years; 20 males and 5 females) who underwent CAS under distal balloon protection. The average rate of carotid stenosis was 74.6 ± 12.9% by North American Symptomatic Carotid Endarterectomy Trial criteria. We assessed culprit plaque components by VH-IVUS before CAS. Aspirated debris was filtered, stained with HE and mounted onto glass slides. The quantity of debris was evaluated by measuring its surface area. We evaluated the relationship between the quantity of aspirated debris and VH-IVUS measurements before CAS. Results: The amount of debris during CAS was positively correlated with the total plaque volume in grayscale IVUS (Rs = 0.480, p = 0.015) and fibro-fatty volumes over the entire lesion length in VH-IVUS (Rs = 0.561, p = 0.001). Conclusions: Culprit lesions with large plaque volumes, especially larger fibro-fatty volumes, as imaged by VH-IVUS, are associated with large amounts of debris during balloon-protected CAS.

Calcified ball thrombus in the left atrium

We experienced a case of calcified ball thrombus that was fixed to the atrial septum in the left atrium. This patient had no symptoms and no cardiac dysfunction. the thrombus was detected during preoperative work-up of a retroperitoneal tumor. The process of fixation to the atrial septum and calcification is unclear.

Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: Report of a case

We report a case of undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi. A 73-year-old man presented with general malaise. Abdominal computed tomography and magnetic resonance imaging revealed a mass in the distal common bile duct, accompanied by dilatation of the intra- and extrahepatic bile ducts. The patient underwent pancreaticoduodenectomy with regional lymphadenectomy. Gross examination revealed that the distal common bile duct was obstructed by an elastic hard mass, 3.2 × 2.6 cm, accompanied by intraductal tumor thrombi. Microscopically, the nodule was well defined and composed of atypical large tumor cells with bizarre nuclei and little cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin-7 and CAM5.2, but negative for CD56, chromogranin A, and synaptophysin. Thus, a histological diagnosis of undifferentiated carcinoma of the common bile duct was made. The patient recovered uneventfully and has remained free of any signs of recurrence for 18 months since the operation. Undifferentiated carcinomas of the extrahepatic bile duct can be detected early, with the chance of a good prognosis; however, because their biologic growth behavior is still considered aggressive, careful observation after surgery and the initiation of multidisciplinary treatment against recurrence are necessary.

Inactivation of amyloid-enhancing factor (AEF) : study on experimental murine AA amyloidosis

It is known that amyloid-enhancing factor (AEF) shortens the preamyloid phase in experimentally induced AA amyloidosis in mice. Because it is reported that AEF serves as both a nidus and a template for amyloid formation, AA amyloidosis may have transmissibility by a prion-like mechanism. It has been shown that amyloid fibrils also have AEF activity, and amyloid fibrils with AEF activity were named fibril-amyloid enhancing factor (F-AEF). In this study, we investigated methods to inactivate the AEF activity. AEF was extracted from the thyroid gland obtained at autopsy of a patient with AA amyloidosis. Before injection into mice, AEF was treated with several methods for inactivation. Of all the tested treatments, 1 N NaOH, 0.1 N NaOH, and autoclaving consistently demonstrated complete inactivation of AEF. Heat treatment led to incomplete inactivation, but 0.01 N NaOH, 0.001 N NaOH, pepsin, trypsin, pronase, and proteinase K treatment had no effect on AEF activity. By analysis with transmission electron microscopy, the AEF preparation contains amyloid fibrils, and a change of ultrastructure was shown after 1 N NaOH, 0.1 N NaOH, and autoclaving treatment. Furthermore, immunoblotting of AEF with antihuman AA antibody revealed that the protein band was scarcely found after autoclaving, 1 N NaOH, and 0.1 N NaOH treatment. Our results suggest that, similar to Creutzfeldt–Jakob disease (CJD), amyloidosis may require chemical or autoclaving decontamination.