Dopamine agonists and valvular heart disease in Japanese patients with Parkinson's disease

Journal of Neurology - A high incidence of valvular heart disease in Parkinson's disease (PD) patients treated with ergot-derived dopamine agonists, such as cabergoline and pergolide, has been...     

A Case Report of Inflammatory Pseudosarcoma of the Urinary Bladder

A case of inflammatory pseudosarcoma of the urinary bladder in a 35 year-old Japanese male is presented. This benign lesion can easily be mistaken for spindle cell sarcoma since it consists of rhabdomyoblast like elongated strap cells showing infiltrative growth, and whether it is benign or malignant is difficult to determine by microscopic examination. In this case, spindle cell proliferation extended among bundles of the superficial muscle layer. However, no abnormal mitoses, severe nuclear atypia or cellular pleomorphism could be seen, thus indicating inflammatory pseudosarcoma. Although the lesion was not completely resected, no recurrent disease has been clinically observed for two years following transurethral resection. Urologists and surgical pathologists must be able to detect this lesion in order to avoid unnecessary surgical procedures. Acta Pathol Jpn 42: 760 765,1992.     

Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery]

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.     

Treatment of hyperthyroidism with a small single daily dose of methimazole

A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 +/- 2.8 and 6.0 +/- 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).     

Transoral transclival approach to vertebral-posterior inferior cerebellar artery aneurysm. Case report

A 61-year-old male was hospitalized for subarachnoid hemorrhage. Cerebral angiography revealed a small left vertebral-posterior inferior cerebellar artery aneurysm, 5 mm to the right of the midline and in the lower third level of the clivus--the so-called "no man's land." It was felt that surgery through the lateral suboccipital approach would likely result in neurological deficits, since the aneurysm would be obscured by the tortuous parent artery or the basilar artery. Therefore, the transoral transclival approach was undertaken and the aneurysm was successfully obliterated. Postoperatively, the patient developed transient right hemiparesis and mild meningitis without evidence of liquorrhea, but fully recovered with conservative management. Certain specific sites of aneurysms, as well as excessive tortuosity of the parent artery, are considered to be indications for the transoral transclival approach. Meningitis is the most worrisome complication of this approach, and mortality is high. Effective preventative measures, which were taken in this case, include tight closure of the dura mater and the pharyngeal mucous membrane, use of the smallest possible clip, and continuous cerebrospinal fluid drainage.     

New perspectives on tooth development and the dental stem cell niche

Adult stem cells have the capacity to self-renew and differentiate along multiple lineages in addition to contributing to ongoing tissue maintenance and regeneration after injury. They reside in specific locations called stem cell niches. In biology of the tooth, the discovery of dental epithelial stem cells in continuously growing teeth has been a recent breakthrough. The niche for the adult stem cells of these teeth is formed at the region of the apical end in tooth development. The region possesses a commonly specialized histological structure for the maintenance of adult stem cells and the production of various progenitor cells producing dental tissues. The molecular signals regulating the maintenance and cell fate decision of adult stem cells, such as Notch1, Lunatic fringe, fibroblast growth factor (FGF)-10, are expressed in the epithelial structure and the surrounding mesenchyme. Based on histological and molecular biological studies, we propose a new concept that the eternal tooth buds producing various dental progeny are formed at the apical end in the development of continuously growing teeth, and coin a new term of "apical bud" for indicating this specialized epithelial structure. Furthermore, the relationship between signaling centers and the expression of FGF-10 mRNA as the determinant of morphogenesis is discussed with an emphasis on tooth and limb development, taking note that the expression pattern of FGF-10 is an important key for understanding the mechanisms for the diversity of cusp patterns and between continuous and limited growth.     

Production and release of infectious hepatitis C virus from human liver cell cultures in the three-dimensional radial-flow bioreactor

Lack of efficient culture systems for hepatitis C virus (HCV) has been a major obstacle in HCV research. Human liver cells grown in a three-dimensional radial-flow bioreactor were successfully infected following inoculation with plasma from an HCV carrier. Subsequent detection of increased HCV RNA suggested viral replication. Furthermore, transfection of HCV RNA transcribed from full-length cDNA also resulted in the production and release of HCV virions into supernatant. Infectivity was shown by successful secondary passage to a new culture. Introduction of mutations in RNA helicase and polymerase regions of HCV cDNA abolished virus replication, indicating that reverse genetics of this system is possible. The ability to replicate and detect the extracellular release of HCV might provide clues with regard to the persistent nature of HCV infection. It will also accelerate research into the pathogenicity of HCV, as well as the development of prophylactic agents and new therapy.     

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.     

Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains

Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves as a signalling function that controls a wide variety of cellular processes. To date, two major forms of polyubiquitin chain have been functionally characterized, in which the isopeptide bond linkages involve Lys48 or Lys63. Lys48-linked polyubiquitin tagging is mostly used to target proteins for degradation by the proteasome, whereas Lys63-linked polyubiquitination has been linked to numerous cellular events that do not rely on degradative signalling via the proteasome. Apparently linkage-specific conformations of polyubiquitin chains are important for these cellular functions, but the structural bases distinguishing Lys48- and Lys63-linked chains remain elusive. Here, we report NMR and small-angle X-ray scattering (SAXS) studies on the intersubunit interfaces and conformations of Lys63- and Lys48-linked di- and tetraubiquitin chains. Our results indicate that, in marked contrast to Lys48-linked chains, Lys63-linked chains are elongated molecules with no stable non-covalent intersubunit interfaces and thus adopt a radically different conformation from that of Lys48-linked chains.