Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases. Received: 4 October 1996 / Accepted: 6 December 1996     

Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.     

Increase of soluble Fc gamma RIIIa derived from macrophages in plasma from patients with atherosclerosis

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express Fc gamma RIIIa(CD16) identical to that in NK cells, but with a cell type-specific glycosylation. In contrast, neutrophils express Fc gamma RIIIb in two allotypes, NA1- and NA2- Fc gamma RIIIb. These Fc gamma RIIIs are released from the cell surface on activation, and these soluble forms(sFc gamma RIII) are present in plasma. In the present study, we measured sFc gamma RIIIaM phi in plasma with Immuno-PCR with newly-developed anti-Fc gamma RIII mAb, MKGR14(mIgM), which recognizes Fc gamma RIIIaM phi specifically. In healthy donors, the level of sFc gamma RIIIaM phi increased with age. In contrast, the sFc gamma RIIIa level correlated with the number of NK cells in peripheral blood, and the level of total sFc gamma RIII(sFc gamma RIIIa plus sFc gamma RIIIb) correlated with the number of neutrophils. There was no correlation among the levels of three sFc gamma RIIIs was observed in healthy donors. The levels of these sFc gamma RIII were significantly increased in patients with coronary artery disease (CAD) compared with age-matched healthy donors. The sFc gamma RIIIaM phi level was related to the number of significant coronary artery stenoses, and correlated with the sFc gamma RIIIa level, total cholesterol, HDL-cholesterol(negatively), LDL to HDL ratio, triglycerides and body mass index. These findings may show that the macrophages are activated during the incipient stage of atherosclerosis, and that sFc gamma RIIIaM phi may serve as predictive marker for atherosclerosis.     

Mcm1 regulates donor preference controlled by the recombination enhancer in Saccharomyces mating-type switching

Switching of Saccharomyces mating type by replacement of sequences at the MAT locus involves a choice between two donors, HML and HMR. MATα cells inhibit recombination along the entire left arm of chromosome III, including HML, whereas MATa cells activate this same region. MATa-dependent activation of HML depends on a small, cis-acting DNA sequence designated the recombination enhancer (RE), located 17 kb centromere-proximal to HML. A comparison of RE sequences interchangeable between Saccharomyces cerevisiae and Saccharomyces carlsbergensis defines a minimum RE of 244 bp. RE activity is repressed in MATα cells by binding of the Matα2–Mcm1 corepressor to a site within the RE. Mutation of the two Matα2 binding sites removes most, but not all, of this repression, and RE chromatin structure in MATα cells becomes indistinguishable from that seen in MATa. Surprisingly, a 2-bp mutation in the Mcm1 binding site completely abolishes RE activity in MATa cells; moreover, RE chromatin structure in the MATa mutant becomes very similar to that seen in MATα cells with a normal RE, displaying highly ordered nucleosomes despite the absence of Matα2. Further, a mutation that alters the ability of Mcm1 to act with Matα2 in repressing a-specific genes also alters donor preference in either mating type. Thus, Mcm1 is critically responsible for the activation as well as the Matα2-Mcm1-mediated repression of RE activity.     

Two cases of limited cutaneous nodular amyloidosis with primary Sj?gren's syndrome]

We described two female patients with primary Sj?gren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sj?gren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sj?gren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sj?gren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.     

Mental component of health-related quality of life is an independent predictor of incident functional disability among community-dwelling older people: a prospective cohort study

Quality of Life Research - Previous studies have reported a positive association between poor health-related quality of life (HRQOL) and disability mainly in relation to the physical component of...     

A study of comparison between the nationwide epidemiological survey in 1991 and previous surveys on behçet’s disease in Japan

The 4th nationwide epidemiological survey on Behçet disease (BD), which included all patients with BD at 1,200 hospitals selected at random from 10,081 hospitals in Japan, was carried out by the BD Research Committee of the Ministry of Health and Welfare in 1991 to examine the epidemiological features of BD in Japan by comparing with previous surveys. 3,938 patients from these hospitals were examined by the Japanese diagnostic criteria of BD (JCBD) revised in 1987 and the International criteria for classification of BD (ICBD). Among these 3,938 patients, 622 patients were only suspected of having BD or clinical signs of the disease were unknown, and most of these patients were incompatible with the ICBD. So these patients were excluded from the study of epidemiological features. The average patients age has risen 7–8 years over the last 20 years and the average age of onset in both sexes increased by about 3 years from 1972 to 1991. While a decrease in the sex ratio was seen in the complete-type and the incomplete-type BD without ocular symptoms, a sustained high sex ratio was shown in incomplete-type BD with ocular symptoms. The positive rate of HLA-B51 antigen was 54.9% (men: 56.9%, women: 52.2%) significantly higher than die 15–16% in healthy subjects but it might have been gradually decreasing. Also the clinical course of BD has become too mild for prognosis. According to diese epidemiological features of BD, the clinical manifestation of BD in Japan might have become the Western type of BD.     

Historical and pathological overview of Castleman disease

Castleman disease consists of several lymphoproliferative subtypes that share some histological features in the lymph nodes. On the other hand, numerous clinical findings and etiologies make the disease challenging to understand. The origin of the disease is the hyaline vascular-type unicentric Castleman disease (UCD), first reported by Benjamin Castleman et al. in 1954. Although UCD is characterized by localized lesions and lack of symptoms, multicentric Castleman disease (MCD) with multiple lesions and systemic symptoms was reported by Frizzera in 1983. MCD is further divided according to KSHV/HHV8 infection status. In KSHV/HHV8-related MCD, viral infection signals lead to excessive cytokine production, and cause clinical and pathologic abnormalities. Some cases of plasma cell-type KSHV/HHV8-negative MCD can be found in association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin changes), which is a paraneoplastic syndrome. The others are idiopathic MCD, which are currently considered a heterogeneous group of diseases with overlapping pathological and clinical features. In this article, we summarize the historical evolution of Castleman disease to help understand the disease concept. We also review the latest ideas and definitions of the subtypes within the MCD spectrum and summarize the histopathological findings.     

Role of chymase on growth of cultured canine Tenon's capsule fibroblasts and scarring in a canine conjunctival flap model

Chymase is a chymotrypsin-like serine protease contained in the secretory granules of mast cells. Recently, we reported that chymase activity and the number of chymase-positive mast cells in conjunctival tissues were significantly increased during the wound healing process in a hamster model of glaucoma surgery. However, it has been unclear the role of chymase on conjunctival scarring. In the present study, we evaluated the effect of dog chymase on cell proliferation of fibroblasts established from canine Tenon's capsule and the effect of a chymase inhibitor on scarring in a canine conjunctival flap model. After a fibroblast cell culture was established from canine Tenon's capsules, the fibroblasts were incubated in the presence of dog chymase (5-20 ng ml(-1)). Cell proliferation was evaluated by bromodeoxyuridine incorporation. In a canine conjunctival flap model, a sponge treated with a chymase inhibitor, Suc-Val-Pro-Phe(P)(OPh)(2), or placebo was placed in between the conjunctiva and sclera and the conjunctival incision was closed. One week after the surgery, adhesion degree was assessed, and chymase activities in the conjunctival lesion and in the areas of the conjunctiva and sclera were measured. In cultured canine Tenon's capsule fibroblasts, dog chymase significantly increased cell proliferation, and this chymase-dependent proliferation was completely suppressed by the chymase inhibitor. In the canine surgical model, chymase activity in placebo-treated eyes was significantly increased compared to control eyes, while it was significantly decreased by treatment with the chymase inhibitor. Scores for adhesion degree in the chymase inhibitor-treated eyes were significantly decreased in comparison with those in placebo-treated eyes. The conjunctival area in the chymase inhibitor-treated eyes was also suppressed to 52.6% compared with that in placebo-treated treated eyes. In conclusion, chymase stimulates proliferation of fibroblasts derived from canine Tenon's capsule and chymase may play an important role in scarring after glaucoma surgery.