Sézary syndrome managed with histone deacetylase inhibitor followed by anti-CCR4 monoclonal antibody.

A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cß1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis. Anti-CCR4 monoclonal antibody (mogamulizumab) treatment was started. After seven courses, the CCR4-positive atypical lymphocytes decreased in the dermis to levels below those seen at the outset of treatment. To our knowledge, there is no previous report of a case of SS managed with vorinostat followed by mogamulizumab demonstrating such a remarkable change in the pathological state following treatment.

Clinical and immunological profiles in 17 Japanese patients with drug-induced pemphigus studied at Kurume University.

BACKGROUND: Drug-induced pemphigus (DIP) shows clinical, histopathological and immunological features of pemphigus. However, little is known about immunological profiles in DIP. OBJECTIVES: To characterize clinical and immunological profiles in patients with DIP. METHODS: We studied 17 Japanese patients with DIP who were treated at Kurume University Hospital or who consulted from other hospitals between 1997 and 2012. Complicated diseases, clinical and histopathological manifestations, responsible drugs and findings in immunofluorescence, enzyme-linked immunosorbent assays (ELISAs), immunoblotting (IB) and prognosis were analysed. RESULTS: Eight of the 17 patients with DIP showed pemphigus foliaceus-like appearance, three showed pemphigus herpetiformis-like appearance, and six showed atypical bullous lesions. Responsible drugs were thiol-containing drugs in 16 patients (bucillamine in nine cases, d-penicillamine in four cases, and cetapril, thiopronine and captopril in one patient each), and a nonthiol drug, sulfasalazine, in one patient. By ELISAs and/or IB analyses, nine patients reacted only with desmoglein 1 (Dsg1), four reacted with Dsg1 and Dsg3, and four showed no specific reactivity. By IB of normal human epidermal extracts, in addition to positive reactivity with Dsg1, four patients with no detectable malignancy showed paraneoplastic pemphigus-like reactivity with the 210-kDa envoplakin and the 190-kDa periplakin. Four cases showed anti-Dsg3 antibodies without mucosal lesions. While 11 cases recovered after discontinuation of the causative drugs, six patients had a very protracted or intractable disease course, and might develop true pemphigus. CONCLUSIONS: The present study indicated that the majority of the patients with DIP studied showed a pemphigus foliaceus-type phenotype with anti-Dsg1 autoantibodies, caused by thiol-containing drugs.

Extranodal natural killer/T-cell lymphoma from skin or soft tissue: suggestion of treatment from multinational retrospective analysis.

BACKGROUND: Clinical features and outcomes of extranodal natural killer/T-cell lymphoma (ENKL) arising from extranasal sites are not fully understood. The purpose of this study was to study the prognosis and treatment outcome of skin/soft tissue primary ENKL. PATIENTS AND METHODS: This multicenter retrospective study included 48 patients with skin/soft tissue primary ENKL diagnosed from 1993 to 2010. RESULTS: Patients with Ann Arbor stage I, T1-2N0M0 by International Society for Cutaneous Lymphomas-European Organization of Research and Treatment of Cancer TNM (tumour-node-metastasis) stage, International prognostic index score of 0-1, and a Korean prognostic index (KPI) score of 0-1 were associated with better survival. Four of five patients with T1-2N0M0 disease achieved complete response with radiation alone. In disseminated disease, only 6 of 13 patients responded to anthracycline-containing chemotherapy, and all the two patients receiving SMILE showed response. CONCLUSION: In conclusion, we identified the prognostic value of KPI, and we suggest a treatment recommendation according to the TNM (tumour-node-metastasis) stage. Radiotherapy with/without chemotherapy seemed to be optimal in localized disease. In advanced stages, a more aggressive treatment regimen with newer agents should be sought.

Endoscopic third ventriculotomy improves parkinsonism following a ventriculo-peritoneal shunt in a patient with non-communicating hydrocephalus secondary to idiopathic aqueduct stenosis.

We report a 47-year-old woman who manifested ocular motility disorder, bilateral pyramidal signs, and severe parkinsonism after a ventriculo-peritoneal shunt for non communicating hydrocephalus secondary to idiopathic aqueduct stenosis. The ocular motility disorder consisted of severe vertical gaze palsy and convergence retraction nystagmus. Parkinsonism included not only bradykinesia but also resting tremor and cogwheel rigidity. On the other hand, striatal uptake did not decrease in (18)F-dihydroxyphenylalanine positron emission tomography, and anti-Parkinsonian drugs were not effective. 99mTc-ethyl cysteinate dimer bicisate single-photon emission computed tomography and F-18 fluorodeoxyglucose positron emission tomography revealed wide-ranged frontal cerebral cortical dysfunction due to midbrain dysfunction. Moreover, endoscopic third ventriculotomy markedly improved the clinical symptoms as well as the frontal cerebral cortical flow. A neural network formation known as the 'cortico-basal ganglia loop,' which intimately connects the frontal lobe with the basal ganglia, is possibly associated with the Parkinsonism observed in our patient.

Pool of dust particles over the Asian continent: balloon-borne optical particle counter and ground-based lidar measurements at Dunhuang, China.

Measurements of aerosols were made in 2001 and 2002 at Dunhuang (40 degrees 00'N, 94 degrees 30'E), China to understand the nature of atmospheric particles over the desert areas in the Asian continent. Balloon-borne measurements with an optical particle counter suggested that particle size and concentration had noticeable peaks in super micron size range not only in the boundary mixing layer but also in the free troposphere. Super-micron particle concentration largely decreased in the mid tropopause (from 5 to 10 km; above sea level, a.s.l.). Lidar measurements made during August 2002 at Dunhuang suggested the possibility that mixing of dust particles occurred from near the ground to about 6 km even under calm weather conditions, and a large depolarization ratio of particulate matter was found in the aerosol layer. The top of the aerosol layer was found at heights of nearly 6 km (a.s.l.). It is strongly suggested that nonspherical dust particles (Kosa particles) frequently diffused in the free atmosphere over the Taklamakan desert through small-scale turbulences and are possible sources of dust particles of weak Kosa events that have been identified in the free troposphere not only in spring but also in summer over Japanese archipelago. Electron microscopic experiments of the particles collected in the free troposphere confirmed that coarse and nonspherical particles observed by the mineral particle were major components of coarse mode (diameter larger than 1 microm) below about 5 km over Dunhuang, China.

Expression of Ki-67 antigen and vascular endothelial growth factor in sporadic and neurofibromatosis type 2-associated schwannomas.

Neurofibromatosis type 2 (NF2) is a formidable disease with considerable morbidity. Among tumors associated with NF2, schwannomas are the most difficult to treat because they are multiple and tend to recur. Vascular endothelial growth factor (VEGF) has been reported to act as a survival factor for Schwann cells. We, therefore, investigated VEGF expression in NF2-associated and sporadic schwannomas. We also evaluated the proliferative potential of these tumors by Ki-67 staining (MIB-1 labeling index) and microvascular density by CD34 staining. Immunohistochemistry was performed in 8 schwannomas from 6 NF2 patients, 2 schwannomas from 2 probable NF2 patients and 10 sporadic schwannomas. VEGF immunostaining was present in most schwannomas: all sporadic schwannomas and 8 of 10 schwannomas from NF2 or probable NF2 patients (NF2 group). No difference was evident in VEGF staining between the 2 groups. MIB-1 labeling index was significantly higher in the NF2 group (3.8 +/- 1.7) than the sporadic group (2.0 +/- 1.0, p < 0.01). Microvascular density was higher in the NF2 group (12.9 +/- 6.0) than the sporadic group (9.4 +/- 3.5), but not significantly (p = 0.06). Although VEGF alone cannot explain the higher proliferative potential in NF2-associated schwannomas, VEGF could be a factor influencing the proliferative potential of schwannomas.

Treatment of a sphenoid sinus mucocele using an endoscope combined with a navigating system: a case report.

A sphenoid sinus mucocele extending into the middle cranial fossa and the pterygomaxillary fissure was decompressed using an endoscope in combination with a navigation system. A 59-year-old woman was admitted with a 3 month history of retro-ocular pain and right sided exophthalmos. To evaluate the cystic lesion, a fibreoptic endoscope was inserted into the cyst through an erosive defect in the temporal bone. The histopathological appearance of cyst wall tissue confirmed the diagnosis of mucocele. After 4 months, the mucocele had refilled and the exophthalmos had recurred. At reoperation, the cyst was fenestrated using a rigid endoscope combined with a navigation system inserted via a sublabial transmaxillary approach. The proper site of cyst fenestration was precisely determined using the navigation system, permitting complete evacuation of this large lesion with minimal invasiveness.

Enhancement and stabilization of traffic flow by moving in groups.

We study the traffic behavior of vehicles moving in groups analytically and numerically. A car-following model of traffic is extended to take into account a binary mixture of vehicles. It is shown that the movement in groups stabilizes the traffic flow. The jamming transition among the free traffic, the inhomogeneous traffic, and the homogeneous congested traffic occurs at a higher density than the threshold of the original model. The traffic current is highly enhanced at a high-density region by keeping a short headway without jam. The jamming transition is analyzed by using the linear stability method. It is found that the theoretical neutral stability curve agrees with the transition line obtained by the simulation.

Transmembrane ion channels constructed of cholic acid derivatives.

A new class of supramolecular transmembrane ion channels was prepared by linking two amphiphilic cholic acid methyl ethers through biscarbamate bonds to afford bis(7,12-dimethyl-24-carboxy-3-cholanyl)-N,N'-xylylene dicarbamate 2 and bis[7,12-dimethyl-24-(N,N,N-trimethylethanaminium-2-carboxylate)-3-cholanyl]-N,N'-xylylene dicarbamate dichloride 3. When incorporated into a planar bilayer membrane, both compounds showed stable (lasting 10 ms to 10 s) single ion channel currents. Only limited numbers of relatively small conductances were characterized for these channels (5-20 pS for 2 and 5-10 pS for 3, 10 and 17 pS for 2, and 9 pS for 3 in particular). Both channels were cation selective, and permeability ratios of potassium cation to chloride anion were 17 and 7.9 for 2 and 3, respectively, reflecting the difference in ionic species of the headgroup. Both channels 2 and 3 showed significant potassium selectivity over sodium by a factor of 3.1 and 3.2, respectively. No Li(+) currents were observed for 2, showing sharp discrimination between Na(+) or K(+).

Anticonvulsant hypersensitivity syndrome associated with reactivation of cytomegalovirus.

Recently, it has been proposed that viral infection is involved in the pathogenesis of hypersensitivity syndrome. Cytomegalovirus (CMV), one of the aetiological agents of infectious mononucleosis, has never been reported as an organism associated with hypersensitivity syndrome. We describe a 64-year-old man with severe phenytoin-induced hypersensitivity syndrome associated with CMV infection. Twenty-five days after the patient was started on phenytoin, he developed high fever and a generalized erythematous rash followed by jaundice, renal failure and disseminated intravascular coagulopathy (DIC). CMV-specific IgG antibodies were significantly increased 7 weeks after the onset of clinical symptoms and the increase was associated with the appearance of CMV-specific IgM. CMV DNA was detected in the serum of the patient. Coinfection with other viruses, such as Epstein-Barr virus and human herpesviruses 6 and 7, could be excluded because antibody titres to those viruses did not increase during the clinical course of his illness. We suggest that reactivation of CMV may contribute, at least in some cases, to the development of hypersensitivity syndrome.

Bunching transition in a time-headway model of a bus route.

A time-headway model is presented to mimic bus behavior on the bus route. The motion of a bus is described in terms of the time headway between its bus and the bus in front. We study the bunching behavior of buses induced by interacting with other buses and passengers. It is shown that the dynamical phase transitions among the inhomogeneous bunching phase, the homogeneous free phase, the coexisting phase, and the homogeneous congested phase occur with varying the initial time headway. We study the effect of not stopping at bus stops on the time-headway profile. It is found that the bunching transition lines are consistent with the neutral stability curves obtained by the linear stability analysis.

Traffic jams induced by fluctuation of a leading car.

We present a phase diagram of the different kinds of congested traffic triggered by fluctuation of a leading car in an open system without sources and sinks. Traffic states and density waves are investigated numerically by varying the amplitude of fluctuation using a car following model. The phase transitions among the free traffic, oscillatory congested traffic, and homogeneous congested traffic occur by fluctuation of a leading car. With increasing the amplitude of fluctuation, the transition between the free traffic and oscillatory traffic occurs at lower density and the transition between the homogeneous congested traffic and the oscillatory traffic occurs at higher density. The oscillatory congested traffic corresponds to the coexisting phase. Also, the moving localized clusters appear just above the transition lines.

Density waves in traffic flow.

Density waves are investigated in the car-following model analytically and numerically. This work is a continuation of our previous investigation of traffic flow in the metastable and unstable regions [Phys. Rev. E 58, 4271 (1998); 60, 180 (1999)]. The Burgers equation is derived for the density wave in the stable region of traffic flow by the use of nonlinear analysis. It is shown, numerically, that the triangular shock wave appears as the density wave at the late stage in the stable region. The decay rate of the shock wave is calculated and compared with the analytical result. It is shown that the density waves out of the coexisting curve, near the spinodal line, and within the spinodal line appear, respectively, as the triangular shock wave, the soliton, and the kink-antikink wave. The density waves are described, respectively, by the Burgers, Korteweg-de Vries, and modified Korteweg-de Vries equations.

Cutaneous monomorphous CD4- and CD56-positive large-cell lymphoma.

BACKGROUND: Recently, CD56 (NCAM)-positive lymphomas, such as nasal and nasal-type angiocentric NK/T cell lymphoma, aggressive NK cell leukemia/lymphoma and blastic NK cell lymphoma, were described by several authors as a unique group of lymphoma. OBJECTIVE: In this study, we intend to clarify the clinicopathological features of cutaneous CD4+ and CD56+ lymphoma. METHODS: Four patients with cutaneous CD4+ and CD56+ lymphoma were studied. RESULTS: Age at the first examination ranged from 71 to 89 years (mean = 81.2 years). One patient was female and 3 were males. The organ mainly involved at presentation was the skin. Lymphadenopathy, splenomegaly, leukemic spread and central nervous system involvement were observed as the disease progressed. The mean survival time was 12.2 months. Epstein-Barr virus was not detected within the tumor cells. CONCLUSION: This peculiar lymphoma is different from nasal and nasal-type angiocentric NK/T cell lymphoma and aggressive NK cell leukemia/lymphoma. Similar cases have been reported as blastic NK cell lymphoma/leukemia.

Clinical safety and performance of Sugita titanium aneurysm clips.

BACKGROUND: In spite of advantages for neuro-imaging, titanium aneurysm clips are not yet chosen for routine use for clipping of intracranial aneurysms, probably because their reliability has not been demonstrated in large numbers of cases. We assess reliability and safety of Sugita titanium aneurysm clips for routine clinical use in a large number of operated cases. METHOD: Intra-operative performance and safety of Sugita titanium aneurysm clips were evaluated in 347 patients in our institutions. Aneurysms in 261 patients had ruptured: 86 patients had unruptured aneurysms. RESULTS: A total of 441 clips of 52 different types were used. No early or delayed complications occurred in relation to the titianium clips, such as deformity or slippage of a clip. Patient outcome according to the Glasgow Outcome Scale was similar to that when conventional cobalt-based aneurysm clips were used. INTERPRETATION: Reliability and safety of Sugita aneurysm clips were demonstrated in a large number of patients. The clips are suitable for routine use in aneurysm surgery.

Idiopathic hypertrophic cranial pachymeningitis: clinicoradiological spectrum and therapeutic options.

OBJECTIVE: Idiopathic hypertrophic cranial pachymeningitis is a rare disease, of undetermined pathogenesis, that is characterized by inflammation and fibrosis of the dura mater. METHODS: We encountered six patients with idiopathic hypertrophic cranial pachymeningitis and analyzed their clinical presentations, radiological findings, and treatment. RESULTS: In the six patients, the main manifestations were cranial nerve palsies and headache. Three associations were present, namely optic neuropathy, Tolosa-Hunt syndrome, and diabetes insipidus. Gadolinium-enhanced magnetic resonance imaging was diagnostic, showing intense dural enhancement in a linear or nodular pattern. The responses to corticosteroid therapy were better for patients who exhibited linear, rather than nodular, dural enhancement. For one patient, surgical decompression of the superior orbital fissure provided lasting relief. The course of the disease followed one of three patterns, i.e., sustained remission, relapse with corticosteroid independence, or relapse with corticosteroid dependence. Pulse corticosteroid therapy provided significant relief, while reducing the daily corticosteroid requirement and avoiding side effects, for a corticosteroid-dependent relapsing patient. CONCLUSION: Idiopathic hypertrophic cranial pachymeningitis exhibits varied clinical courses. It is important to prevent irreversible cranial neuropathy during the active phase of the disease, using daily administration of corticosteroids, pulse corticosteroid therapy, or surgical decompression.

Role of anchor residues in peptide binding to three HLA-A26 molecules.

To investigate the role of anchor residues in HLA-A26 binding peptides, we analyzed the binding of various peptides to three HLA-A26 molecules using the HLA class I stabilization assay. Of twenty nonamer peptides carrying anchors at P2 and P9, 3, 6 and 3 peptides bound to HLA-A*2601, HLA-A*2602 and HLA-A*2603, respectively The peptide EV-IPMFSAL bound most strongly to these three HLA-A26 molecules. Analysis using mutants of this peptide at P1, P2 or P9 showed that acidic amino acids at P1 and five hydrophobic residues (Val, Thr, Ile, Leu and Phe) at P2 are anchor residues for the three HLA-A26 molecules while with exception of positively charged amino acids, a broad range of amino acids function as P9 anchor residues. These anchors were further evaluated using 38 nonamer peptides carrying anchor residues at P1, P2 and P9. Nineteen of these peptides bound to at least one HLA-A26 molecule. The frequency of HLA-A26 binding peptides was higher for peptides carrying all three anchor residues than for peptides carrying only P2 and P9 anchor residues. These results indicate that in addition to P2 and P9 anchors, the P1 anchor plays an important role in peptide binding to three HLA-A26 molecules.

Perforating branches from offending arteries in hemifacial spasm: anatomical correlation with vertebrobasilar configuration.

OBJECTIVE: In microvascular decompression for hemifacial spasm, the perforating branches around the facial nerve root exit zone occasionally complicate facial nerve decompression. In this context, the vertebrobasilar configuration was retrospectively correlated with the perforating branches. METHODS: Based on vertebral angiography, magnetic resonance angiography, and three dimensional computed tomographic angiography, 69 patients were divided into three groups, according to the anatomy of the vertebrobasilar system. In patients with the type I configuration, the vertebral artery on the affected side was dominant and had a sigmoidal course. The type II patients had the basilar artery curving mainly towards the affected side. The type III patients showed the basilar artery either running straight or curving toward the unaffected side. The relation of the anatomical configuration of these vessels with the perforating branches around the facial nerve exit zone was investigated. RESULTS: The posterior inferior cerebellar artery in type I patients (n=33) and the anterior inferior cerebellar artery in type II (n=5) and type III (n=31) patients were the most common offending arteries. More than half of the type I patients (n=20) showed no perforating branches around the facial nerve exit zone. However, the type II (n=3) and III patients (n=23) often showed one or more perforating branches around that region. CONCLUSIONS: The configuration of the vertebrobasilar system has a significant correlation with the presence of perforating branches near the site of microvascular decompression. These perforating vessels are often responsible for the difficulty encountered in mobilising the offending artery during the procedure.

Detection and sequence diversity of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) DNA.

Detection of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV)/human herpesvirus (HHV-8) has been reported frequently in patients with KS associated with acquired immunodeficiency syndrome (AIDS). We examined the presence of the KSHV sequence in 8 HIV-positive patients comprising 5 with KS, 2 with syphilis, 1 with prurigo, and 2 HIV-negative patients with angiosarcoma. Using the polymerase chain reaction, we observed amplification of a DNA fragment of the expected size in 4 patients with KS. Sequencing analysis of the amplified fragments revealed several base substitutions upon comparison with the originally reported sequence. Our results support the hypothesis of a pathogenic role of KSHV in the development of skin lesions in HIV-positive patients with KS, and the sequences of KSHV DNA fragments isolated in this study also demonstrated strain diversity similar to that reported previously.