Multipole polaron in the devil's staircase of CeSb.

Rare-earth intermetallic compounds exhibit rich phenomena induced by the interplay between localized f orbitals and conduction electrons. However, since the energy scale of the crystal-electric-field splitting is only a few millielectronvolts, the nature of the mobile electrons accompanied by collective crystal-electric-field excitations has not been unveiled. Here, we examine the low-energy electronic structures of CeSb through the anomalous magnetostructural transitions below the Néel temperature, ~17 K, termed the 'devil's staircase', using laser angle-resolved photoemission, Raman and neutron scattering spectroscopies. We report another type of electron-boson coupling between mobile electrons and quadrupole crystal-electric-field excitations of the 4f orbitals, which renormalizes the Sb 5p band prominently, yielding a kink at a very low energy (~7 meV). This coupling strength is strong and exhibits anomalous step-like enhancement during the devil's staircase transition, unveiling a new type of quasiparticle, named the 'multipole polaron', comprising a mobile electron dressed with a cloud of the quadrupole crystal-electric-field polarization.

Devil's staircase transition of the electronic structures in CeSb.

Solids with competing interactions often undergo complex phase transitions with a variety of long-periodic modulations. Among such transition, devil's staircase is the most complex phenomenon, and for it, CeSb is the most famous material, where a number of the distinct phases with long-periodic magnetostructures sequentially appear below the Néel temperature. An evolution of the low-energy electronic structure going through the devil's staircase is of special interest, which has, however, been elusive so far despite 40 years of intense research. Here, we use bulk-sensitive angle-resolved photoemission spectroscopy and reveal the devil's staircase transition of the electronic structures. The magnetic reconstruction dramatically alters the band dispersions at each transition. Moreover, we find that the well-defined band picture largely collapses around the Fermi energy under the long-periodic modulation of the transitional phase, while it recovers at the transition into the lowest-temperature ground state. Our data provide the first direct evidence for a significant reorganization of the electronic structures and spectral functions occurring during the devil's staircase.

Identification of the hexon region of an adenovirus involved in a new outbreak of keratoconjunctivitis.

We tested 15 adenovirus (Ad)-positive patients involved in a case of nosocomial spread of keratoconjunctivitis. A neutralization test, PCR-restriction fragment length polymorphism analysis, and sequencing of the hypervariable regions of the hexons were performed in order to identify the type of Ad involved. The serotype of the Ad was not identical to any published Ad sequence by either method.

Uveitopathogenic sites in recoverin.

PURPOSE: This study was carried out in order to determine the most potent and novel uveitopathogenic sites of recoverin using synthetic peptides. METHODS: Several synthetic peptides containing the recoverin sequence plus adjuvants were injected into Lewis rats, and the uveitopathogenic sequence was defined, clinically, histologically, and immunologically. RESULTS: Peptides containing of amino acids 57-85 and 136-167 induced severe EAU, and the lowest doses to induce EAU were 20 microg and 10 microg, respectively. Lymphocyte proliferative reactions were also positive for peptides 57-85 and 136-167. The core sequences within the uveitopathogenic site were 65-79 and 153-164. Peptides of amino acids 65-79 within 57-85 and 149-167 within 136-167 were the smallest in the recoverin sequence, respectively, that could induce severe EAU. CONCLUSION: We found recoverin has some novel potent uveitopathogenic sites, 149-167. These findings of the uveitopathogenic sites in recoverin may lead to improved understanding of the pathogenesis of uveitis and the means to design specific treatment.

Fas expression and apoptosis in rats with experimental autoimmune uveoretinitis.

PURPOSE: To evaluate Fas expression on CD4 and CD8 T cells in each organ at each stage of experimental autoimmune uveoretinitis (EAU) and apoptotic cells within EAU eyes. METHODS: Rats were immunized with the uveitopathogenic peptide derived from interphotoreceptor retinoid-binding protein. Flow cytometry was performed in ocular cells, draining lymph nodes cells and splenic cells of EAU rats to investigate Fas expression by CD4 and CD8 lymphocytes. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining of apoptotic nuclei was performed on sections of EAU eyes. RESULTS: Fas expression by both ocular and splenic CD4 and CD8 lymphocytes was significantly higher than in lymph nodes at each stage. In EAU eyes, there was a relatively large population of lymphocytes with Fas expression (19.6-25.6% of CD4 and 33.2-53.4% of CD8). Apoptotic cells were more prominent in the EAU eyes with established disease than in those with early or resolving disease. CONCLUSIONS: These results suggest that the relatively large population of lymphocytes with Fas expression in EAU eyes reflects the activation of lymphocytes in these eyes, and that the increase in apoptotic inflammatory cells at the peak of established disease may participate in the spontaneous disappearance of EAU.

Hypervascular liver metastasis from hypovascular ductal cell carcinoma of the pancreas.

In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.

Suppression of experimental autoimmune uveoretinitis by dietary calorie restriction.

To investigate the inhibitory effect of dietary calorie restriction on experimental autoimmune uveoretinitis (EAU) in rats, and its mechanism. Lewis rats were maintained on a 50% calorie-restricted diet for 2 months or 6 months. The control group was maintained on a 90% ad libitum intake for the same length of time. Experimental autoimmune uveoretinitis was elicited in both groups by immunization with an inter-photoreceptor retinoid-binding protein or its peptide. Rats in both groups were examined clinically, histopathologically, and immunologically. The severity of EAU was milder in the restricted diet group than in the control group. In EAU rats, production of interferon-gamma (IFN-gamma) in eyes and of IFN-gamma and tumor necrosis factor-alpha in draining lymph node cells was significantly lower in the restricted diet group than in the control group. Our results indicate that a calorie-restricted diet suppresses the development of EAU. The suppressed Th1-dependent immunological response is one of the reasons for the mildness of EAU in the calorie-restricted diet group of rats.

Uveitopathogenic site of the gamma-subunit of cyclic guanosine monophosphate phosphodiesterase in Lewis rats.

PURPOSE: The gamma-subunit of cyclic guanosine monophosphate phosphodiesterase (PDEgamma) plays an important role in the phototransduction process of rod photoreceptors. A previous report indicated that experimental autoimmune uveoretinitis (EAU) could be induced in Lewis rats by immunization with PDEgamma. In this study, we identified the uveitopathogenic site of PDEgamma synthetic peptides and identified pivotal amino acid residues using analogue peptides. METHODS: Several synthetic peptides derived from PDEgamma plus adjuvants were injected in Lewis rats. The induction of EAU was examined clinically and histologically. In addition, humoral and cellular immunity against peptides was investigated. RESULTS: The smallest uveitopathogenic peptide was identified as PDEgamma 64-76 (ITVICPWEAFNHL), which consists of 13 amino acid residues, and the core sequence was identified as PDEgamma 70-76 (WEAFNHL), which consists of 7 amino acid residues. The lowest dose of peptide to induce EAU was 0.03 nmol. The pivotal amino acid residues for eliciting EAU are at 70(W), 71(E), 73(F), and 75(H). CONCLUSION: Our findings demonstrated the presence of a potent uveitopathogenic site in PDEgamma whose potency in Lewis rats was comparable to that of interphotoreceptor retinoid-binding protein.

Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease (and sympathetic ophthalmia) is an ocular inflammatory disease that is considered to be a cell-mediated autoimmune disease against melanocytes. The purpose of this study was to determine the Ags specific to VKH disease and to develop an animal model of VKH disease. We found that exposure of lymphocytes from patients with VKH disease to peptides (30-mer) derived from the tyrosinase family proteins led to significant proliferation of the lymphocytes. Immunization of these peptides into pigmented rats induced ocular and extraocular changes that highly resembled human VKH disease, and we suggest that an experimental VKH disease was induced in these rats. We conclude that VKH disease is an autoimmune disease against the tyrosinase family proteins.

Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats.

Vogt-Koyanagi-Harada (VKH) disease is an ocular inflammatory disease and is considered to be a cell-mediated, autoimmune disease against melanocytes. To learn more about the mechanisms involved in VKH disease, the identification of the antigens specific to the disease and the development of an animal model are critically important. We have expressed and purified the melanocyte specific proteins, tyrosinase-related protein 1 (TRP1) and 2 (TRP2). Lewis rats developed an ocular and extraocular inflammatory disease 12 days after immunization with TRP1 or TRP2 that was characterized clinically by the infiltration of inflammatory cells and accumulation of massive fibrin in the anterior and posterior chambers of the eye. Histologically, inflammatory cells were found in the anterior and posterior chambers, iris, ciliary body, the choroid, subretinal space and vitreous body. In severe cases, a serous detachment of the retina was observed. In mild cases, focal inflammatory lesions surrounded by normal chorioretinal architecture were observed and the inflammation persisted for more than 42 days after the injection. Some eyes showed accumulation of epithelioid cells in the choroid or the retinal pigment epithelium which were similar to the Dalen-Fuchs nodules found in patients with VKH disease. The alterations of the photoreceptor outer segment and the outer nuclear layer were less severe than in experimental autoimmune uveitis induced by retinal antigens. Extraocular manifestations such as skin lesions and meningitis were also observed. The clinical course and histological findings in these rats resembled the changes in patients with VKH disease.

Lectin cytochemistry of the lacrimal sac epithelium in experimental dacryocystitis.

PURPOSE: To study the glycoconjugates in the lacrimal sac epithelium of Japanese white rabbits with experimentally induced chronic dacryocystitis. METHODS: Chronic dacryocystitis was induced by a subcutaneous injection of albumin followed by an injection of Staphylococcus aureus into the lacrimal sac. The histological appearance of the lacrimal sac was studied using the alcian blue-periodic acid-Schiff sequence. In addition, the specific binding to the lacrimal sac epithelium of Ulex europaeus agglutinin 1, Ricinus communis agglutinin 1, peanut agglutinin, and soybean agglutinin was also studied. RESULTS: Staining with alcian blue-periodic acid-Schiff sequence showed hyperplasia of the goblet cells in the inflamed lacrimal sac epithelium. Lectin cytochemistry revealed specific binding of Ulex europaeus agglutinin 1, Ricinus communis agglutinin 1, peanut agglutinin, and soybean agglutinin to the lacrimal sac epithelium. CONCLUSIONS: These results indicated that the composition of glycoconjugates in the lacrimal sac epithelium is markedly changed in dacryocystitis. There seems to be a fundamental abnormality in glycoconjugate synthesis in the chronically inflamed lacrimal sac epithelium.

Decreased tear lactoferrin concentration in patients with chronic hepatitis C.

BACKGROUND/AIMS: Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C. METHODS: Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed. RESULTS: Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p <0.00048). The cotton thread test results in the chronic hepatitis C group (12.9 (5. 5) mm) were significantly lower than in the control group (17.9 (5. 3) mm; p<0.00048). Also, in the chronic hepatitis C group, tear lactoferrin concentration correlated with the results of the cotton thread test (r = 0.35, p<0.05). CONCLUSION: Chronic hepatitis C patients showed both decreased tear volume, and decreased tear lactoferrin concentration. These findings suggest that there may be dysfunction of the lacrimal glands in patients with chronic hepatitis C, which may account for the mild dry eye.

Investigation of luminal surface structures of rod photoreceptor outer segments by lectin cytochemistry combined with freeze-etching.

The luminal surface of the rod photoreceptor disk membrane was exposed by means of osmotic shock and labeled with ferritin- conjugated concanavalin A. The structural changes of the luminal surface were examined by a freeze-etching procedure with cryoprotectant (methanol). On replicas from freeze-etched membranes with concanavalin A labeling, 6- to 10-nm particles were codistributed with ferritin particles on the luminal surface of the disk membrane. By contrast, there were few ferritin particles or less numerous 6- to 10-nm particles on the corresponding surface without concanavalin A labeling. If 6- to 10-nm particles corresponded to the carbohydrate moiety of rhodopsin, concanavalin A binding might tend to preserve this carbohydrate moiety. These results suggest that the two-dimensional analysis of lectin-induced structural changes of the membrane surface glycoconjugates may become available by lectin cytochemistry combined with freeze-etching.

Interaction between the nucleotide exchange factor Mge1 and the mitochondrial Hsp70 Ssc1.

Function of Hsp70s such as DnaK of the Escherichia coli cytoplasm and Ssc1 of the mitochondrial matrix of Saccharomyces cerevisiae requires the nucleotide release factors, GrpE and Mge1, respectively. A loop, which protrudes from domain IA of the DnaK ATPase domain, is one of six sites of interaction revealed in the GrpE:DnaK co-crystal structure and has been implicated as a functionally important site in both DnaK and Ssc1. Alanine substitutions for the amino acids (Lys-108 and Arg-213 of Mge1) predicted to interact with the Hsp70 loop were analyzed. Mge1 having both substitutions was able to support growth in the absence of the essential wild-type protein. K108A/R213A Mge1 was able to stimulate nucleotide release from Ssc1 and function in refolding of denatured luciferase, albeit higher concentrations of mutant protein than wild-type protein were required. In vitro and in vivo assays using K108A/R213A Mge1 and Ssc1 indicated that the disruption of contact at this site destabilized the interaction between the two proteins. We propose that the direct interaction between the loop of Ssc1 and Mge1 is not required to effect nucleotide release but plays a role in stabilization of the Mge1-Ssc1 interaction. The robust growth of the K108A/R213A MGE1 mutant suggests that the interaction between Mge1 and Ssc1 is tighter than required for function in vivo.

Recurrent varicella-zoster virus retinitis in a patient treated with systemic corticosteroids.

A case of recurrent unilateral varicella-zoster virus (VZV) retinitis is reported. The retinitis was characterized by arteriolitis and retinal necrosis with secondary chorioretinal atrophy localized in the periphery of the supratemporal quadrant of the retina. Polymerase chain reaction analysis of aqueous humor demonstrated VZV DNA in both the initial and recurrent episode. The Goldmann-Witmer coefficient for VZV IgG was elevated. The initial VZV retinitis was successfully treated with acyclovir and corticosteroids. Three years later, high-dose corticosteroids alone were used to treat idiopathic facial nerve palsy. One month after concluding corticosteroids therapy, the VZV retinitis recurred in the same eye, suggesting that administration of the high-dose corticosteroids caused VZV reactivation and induced recurrence of VZV retinitis.

Lectin cytochemical analysis of lacrimal pleomorphic adenomas.

The activity of seven different types of biotinylated lectin were examined in normal and tumorous lacrimal gland tissue. In the normal lacrimal gland tissue, the glandular cells and the tubular epithelium were labeled by maclura pomifera agglutinin (MPA), soybean agglutinin (SBA), and bauhinia purpurea agglutinin (BPA). The myoepithelial cells were stained by griffonia simplicifolia agglutinin 1 (GS1). In the primary pleomorphic adenoma tissue, the epithelial components were labeled by MPA, ulex europaeus agglutinin, SBA, peanut agglutinin, and BPA. The mesenchymal components showed negative labeling. In contrast, the recurrent pleomorphic adenoma tissue showed a positive reaction in the mesenchymal components when GS1 and BPA were used. These results revealed differences in the glycoconjugate composition among normal and tumorous lacrimal gland tissues from patients with primary and recurrent pleomorphic adenomas.

Sialoglycoconjugates in primary and recurrent mixed tumors of lacrimal glands.

We examined the activity of Griffonia simplicifolia II agglutinin (GS2) before and after neuraminidase treatment in 2 cases of primary benign mixed tumor (BMT) and a case of recurrent mixed tumor (MT). Histologically, each type of MT is comprised of epithelial and mesenchymal components. GS2, which showed no binding to either structural component in the primary BMT, was specifically bound to the mesenchymal component in the recurrent MT. After neuraminidase treatment, there was a marked increase in GS2-binding levels in the epithelial component of the primary BMT and in both components of the recurrent MT. These results might reveal a prominent sialylation in the recurrent MT.

Analysis of uveitogenic sites in phosducin molecule.

PURPOSE: Phosducin, a retinal photoreceptor protein, induces experimental autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptides. METHODS: Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC. First, 13 peptides covering the entire sequence of phosducin were synthesized, and each was injected into the hind footpad of Lewis rats for immunization, and induction of EAU was examined clinically and histologically. Next, peptides that appeared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. RESULTS: Of the 13 peptides used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior chamber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and serous retinal detachment was found in cases of severe inflammation. Infiltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino acid sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunized with these peptides also exhibited high value on lymphocyte proliferation assay. CONCLUSION: Phosducin has 5 uveitogenic sites. Among others, one of them has potent and others weak uveitogenicity.

A case of effusive-constructive pericarditis: an efficacy of GD-DTPA enhanced magnetic resonance imaging to detect a pericardial thickening.

A 38-year-old man underwent pericardiectomy because of effusive-constrictive pericarditis. The gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging showed pericardial thickening separate from the effusion, which could not be shown by unenhanced computed tomography. Gd-DTPA enhanced magnetic resonance imaging could be useful for the early detection of effusive-constrictive pericarditis.