Search

Supplementary Figures S1-S4 from Allogeneic MHC Gene Transfer Enhances an Effective Antitumor Immunity in the Early Period of Autologous Hematopoietic Stem Cell Transplantation

Water electrolysis driven by renewable energy can produce clean hydrogen, but its efficiency remains low, in part because of slow kinetics at the anode for the oxygen evolution reaction (OER). Learning from the most active catalysts for the OER, iridium oxides, would be the key to the development and establishment of design guidelines for active and stable OER catalysts. This article reviews in situ or operando spectroscopic and advanced computational studies in the past decade concerning the OER over iridium oxide for both the oxidation of water molecules and hydroxide ions. By collectively reviewing the reported findings, we illustrate the plausible OER catalytic cycles including the dissolution of iridium during the reaction, which at the same time disclosed discrepancies in the proposed mechanisms. Such discrepancies are thought to originate from variations in the experimental conditions employed in those studies, calling for comprehensive and systematic in situ or operando studies in the future. Toward the end, we discuss a recent approach for improving the activity and stability of OER catalysts.

Water electrolysis driven by electrical power generated from renewable energy sources will play a pivotal role in future sustainable societies, which requires adaptation of various reaction conditions as well as electrolyte identities. Regardless, the anodic half-reaction of the oxygen evolution reaction (OER) is considered a kinetic bottleneck. This study provides quantitative description of the OER kinetics based on rigorous microkinetic analyses including Tafel analysis, isotope effects and temperature dependence using an IrOx electrocatalyst in unbuffered solution at varying pH levels. The diffusional constraints of H+/OH− determine three distinctive kinetic regimes in the pH-potential-current relationships: below pH 5, between pH 5 and 10, and above pH 10 at appreciable current densities on the order of 1 mA cm−2. When shifting from alkaline to acidic solution, the complete consumption of local OH− near the electrode surface switches the OER proceeding as the oxidation of OH− to that of the water molecule at pH ~ 11 irrespective of the electrode identity. At pH 5–10, the diffusional constraints of H+ generated via oxidation reaction yield an environment with pH ~ 4 near the electrode surface even prior to the OER, resulting in a bulk pH-independent region for the OER performance. Under this unbuffered near-neutral-pH condition, the isotope effect was diminished for the OER catalysis, which is consistent with the rate-determining step (rds) being the sole electron-transfer step via the formation of O-O bonds, decoupled from proton transfer. This reaction mechanism is distinct from that under more acidic conditions (pH

High current density reaching 1 A cm

Near-neutral pH water electrolysis driven by renewable electricity can reduce the costs of clean hydrogen generation, but its low efficiency and gas crossover in industrially relevant conditions remain a challenge. Here, it was shown that electrolyte engineering could suppress the crossover of dissolved gases such as O

Electrocatalytic processes driven by the renewable electricity will play a pivotal role to achieve sustainable in our society, whereby the thermodynamically stable chemicals are converted into value-added products or energy carriers. For instance, the water electrolysis produces green hydrogen, and the carbon dioxide electrolysis yields commodity chemicals such as ethylene or carbon monoxide.[1] These processes commonly share an anodic half-reaction of oxygen evolution reaction (OER) that requires large overpotentials due to its slow kinetics, leading to the significant loss of overall energy efficiency.[2] This is particularly the case at near-neutral pH,[3] which however is likely the desired condition for electrocatalytic CO2 reduction due to the lessened loss of carbon dioxide via carbonate formation that prevails in alkaline conditions.[4] Toward the large-scale operation of these technologies, it is highly desired to develop an active, stable, and earth-abundant metal based electrocatalyst that catalyzes the OER at near-neutral pH and high current densities. The present study reports on our discovery of the transition metal-based electrocatalysts that efficiently catalyze OER in carbonate buffer electrolyte at near-neutral pH. Firstly, a variety of electrodes were fabricated by electro-deposition of transition metals (manganese, iron, cobalt, copper) on electrochemically activated Ni (ECA-Ni) substrates[5] with nanostructured surface. Their electrocatalytic testing revealed that iron oxide (Fe-O) modified ECA-Ni achieved a current density of 100 mA cm−2 at an overpotential of ca. 280 mV in dense electrolyte of 1.5 mol kg−1 K-carbonate solution and 353 K, whose pH was adjusted to pH 10.5 at 298 K prior to the testing. This pH level was essential to achieve stable operation using the Ni-Fe electrode. Subsequently, group 11 metals of copper, silver, or gold were introduced into Fe-O/ECA-Ni via co-electrodeposition to tailor the nature of active site for improved OER. Remarkably, electrodes of Fe-Cu-O/ECA-Ni and Fe-Au-O/ECA-Ni catalyzed the OER at a rate of 1 A cm−2 and an overpotential of ca. 330 mV, whose figure is comparable to those in extremely alkaline conditions (Figure 1). Long-term and on-off stability testing revealed that the developed electrodes maintained its performance. Our characterization on double-layer capacitance indicated the enlarged surface area of Fe-Cu-O and Fe-Au-O electrodes with respect to the pristine Fe-O counterparts, which partly contributed to the improved OER performance. In addition, ex situ X-ray photoelectron spectroscopy and in situ X-ray absorption spectroscopy concurrently pointed to the presence of stable Fe(III) species for Fe-Cu-O/ECA-Ni, plausibly FeOOH. The present study discovered transition metal based electrocatalysts for the OER at near-neutral pH and high current densities, achieving comparable performance to those in alkaline conditions, which is significant given the merits of near-neutral pH condition for CO2 reduction. These findings represent the potentiality of near-neutral pH electrochemical system on industrial scale, which can help to construct a sustainable society. Reference [1] S. Chu, A. Majumdar, Nature 2012, 488, 294. [2] T. Reier, H. N. Nong, D. Teschner, R. Schlögl, P. Strasser, Adv. Energy Mater. 2017, 7, 1601275. [3] T. Nishimoto, T. Shinagawa, T. Naito, K. Takanabe, ChemSusChem 2021, 14, 1554. [4] J. A. Rabinowitz, M. W. Kanan, Nat. Commun. 2020, 11, 5231. [5] T. Shinagawa, M. T.-K. Ng, K. Takanabe, Angew. Chem. Int. Ed. 2017, 56, 5061. Figure 1

This study reports on the impact of identity and compositions of buffer ions on oxygen evolution reaction (OER) performance at a wide range of pH levels using a model IrOx electrocatalyst. Rigorous microkinetic analysis employing kinetic isotope effects, Tafel analysis, and temperature dependence measurement was conducted to establish rate expression isolated from the diffusion contribution of buffer ions and solution resistance. It was found that the OER kinetics was facile with OH− oxidation compared to H2O, the results of which were highlighted by mitigating over 200 mV overpotential in the presence of buffer to reach 10 mA cm−2. This improvement was ascribed to the involvement of the kinetics of the local OH− supply by the buffering action. Further digesting the kinetic data at various buffer pK a and the solution bulk pH disclosed a trade‐off between the exchange current density and the Tafel slope, indicating that the optimal electrolyte condition can be chosen at a different range of current density. This study provides a quantitative guideline for electrolyte engineering to maximize the intrinsic OER performance that electrocatalyst possesses especially at near‐neutral pH., A buffer for OER: Rigorous microkinetic analysis using the IrOx electrocatalyst reveals that OH− is most likely the reactant for the oxygen evolution reaction (OER) in near‐neutral buffered conditions whereby buffering species function to maintain the concentration of OH−. Digesting the OER kinetic data discloses a trade‐off relationship between the exchange current density and the Tafel slope value, determining the optimal electrolyte condition at a given current density.

Hydrogen production from renewable energy and ubiquitous water has a potential to achieve sustainability, although current water electrolyzers cannot compete economically with the fossil fuel‐based technology. Here, we evaluate water electrolysis at pH 7 that is milder than acidic and alkaline pH counterparts and may overcome this issue. The physicochemical properties of concentrated buffer electrolytes were assessed at various temperatures and molalities for quantitative determination of losses associated with mass‐transport during the water electrolysis. Subsequently, in saturated K‐phosphate solutions at 80 °C and 100 °C that were found to be optimal to minimize the losses originating from mass‐transport at the neutral pH, the water electrolysis performance over model electrodes of IrOx and Pt as an anode and a cathode, respectively, was reasonably comparable with those of the extreme pH. Remarkably, this concentrated buffer solution also achieved enhanced stability, adding another merit of this electrolyte for water electrolysis., Keeping it neutral: Determination and analysis of physicochemical properties revealed that phosphate solutions at neutral pH achieved smaller mass‐transport losses during water electrolysis at higher molalities and temperatures. Electrocatalytic testing demonstrated water electrolysis in saturated phosphate solutions to be comparable to that in extreme pH counterparts at elevated temperatures.

Pilocytic astrocytomas are found predominantly in the pediatric population and are extremely rare in elderly patients. We describe a case of pilocytic astrocytoma in an elderly patient who presented with the symptoms of an enlarged tumoral cyst. A 70-year-old woman was found to have an asymptomatic small solid tumor with a cystic component in the right frontal lobe at "Ningen Dock(medical checkup)of the Brain". She was hospitalized and underwent further examinations including cerebral angiography. At that time, she was opposed to undergoing an operation for tumor removal owing to lack of symptoms. Approximately fourteen years later, she presented with dizziness upon posture conversion and recent memory disturbance. Computed tomography scanning revealed an enlarged cyst in the frontal lobe and perifocal edematous changes. Gadolinium-enhanced magnetic resonance imaging partially revealed the solid tumor and cystic capsule. The solid tumor had not enlarged substantially. The cystic fluid was aspirated and the solid tumor was resected via a frontal transcortical approach. The histological diagnosis was pilocytic astrocytoma without malignant features. After surgery, the patient's symptoms improved and additional therapy was not provided. After a year of postoperative follow-up, the size of the cystic lesion has reduced, and no recurrence of the solid tumor has been observed.

Water electrolysis is a core technology in the conversion of renewable energy to hydrogen, which is useful for energy storage and transportation. Alkaline water electrolysis (AWE) is one of the most suitable technologies because of its low cost and applicability to large-scale production of hydrogen; however, the AWE system exhibits electrode degradation under fluctuating electricity from renewable energy such as solar and wind energies. In this study, we demonstrate the use of a hybrid cobalt nanosheet (Co-ns), comprising brucite-type cobalt hydroxide modified with the tripodal ligand tris(hydroxymethyl)aminomethane, to form a highly stable self-repairing catalyst layer on a nickel anode under cycled potential. The Co-ns is functionalized by organic modification as a self-repairing catalyst with high catalytic activity, high dispersibility in an alkaline electrolyte, and protection of the nickel anode from corrosion. The Co-ns supplied from the alkaline electrolyte forms a catalyst layer via the anodic reaction on the surface of the nickel anode. This catalyst layer is detached under cycled potential simulating the fluctuating electricity of renewable energy; however, it is repaired by the constant current electrolysis simulating the steady state operation of AWE. The reaction between the Co-ns and nickel anode strengthens the connection between the catalyst layer and substrate. Furthermore, the Co-ns is less influential to the activity of a commercial cathode, indicating applicability to the conventional AWE system without changing the manifold structure. Consequently, the specially designed Co-ns catalyst shows great potential as a novel self-repairing function in an AWE system, which will enable stable operation under fluctuating electricity from renewable energy.

Based on intracranial-video electroencephalography (EEG), histopathological features, and postoperative seizure outcome, we elucidated the epileptogenicity in patients with dysembryoplastic neuroepithelial tumor (DNT). Five patients (P1–P5) pathologically diagnosed with DNT underwent intracranial-video EEG to identify the ictal onset zone and irritative zone. We evaluated the correlations of ictal onset zone and irritative zone with the magnetic resonance imaging-visible lesion (MRI-lesion) and their histopatho-logical features. Intracranial-video EEG located the ictal onset zone adjacent to the MRI-lesion margin in four patients with complex/simple forms of DNT subcategory, and on the MRI-lesion in P3 with a nonspecific DNT form. The irritative zone extended to surrounding regions of the ictal onset zone in all patients. Histopathologically, MRI-lesions were characterized by specific glioneuronal elements, whereas the ictal onset zone and irritative zone were represented with dysplastic cortex accompanying oligodendroglia-like cells in four (P1, P2, P4, and P5) of five patients. Cortical dysplasia was identified with typical histopathologic features in the irritative zone remote from the MRI-lesion in P5. P3, with a nonspecific form, indicated prominent component of dysplastic cortex with oligodendroglia-like cells scattered in the MRI-lesion. Lesionectomy of MRI-lesion with additional cortical resections (including the ictal onset zone and irritative zone) yielded postoperative seizure freedom (Engel Class I) in P3, P4, and P5, while P1 and P2 (with only lesionectomy) experienced postoperative residual seizure (Class II and III in each patient). Our results suggest the intrinsic epileptogenicity of DNT. The topographical correlation indicated that the dysplastic cortex accompanying oligodendroglia-like cells was more epileptogenic than the specific glioneuronal elements itself. Meticulous intracranial-video EEG analysis delineating the MRI nonvisible ictal onset zone and the irritative zone may yield better seizure outcome.

Alveolar liquid clearance, which mainly depends on sodium transport in alveolar epithelial cells, is an important mechanism by which excess water in the alveoli is reabsorbed during the resolution of pulmonary edema. In this study, we examined the regulation of epithelial sodium channel (ENaC), the main contributor to sodium transport, during acute lung injury and the direct impact of tumor necrosis factor-alpha (TNF-alpha), one of the important cytokines in acute lung injury, on the ENaC regulation. During the development of pulmonary edema, the increases in the number of neutrophils and the levels of TNF-alpha in blood and bronchoalveolar lavage were seen. In parallel, the mRNA expression of the alpha-, beta- and gamma-ENaC subunits in the whole lung tissue was inhibited to 72.0, 47.8 and 53.9%, respectively. The direct exposure of rat alveolar type II cells to TNF-alpha inhibited the mRNA expression of alpha- and gamma-ENaC to 64.0 and 78.0%, but not that of the beta-ENaC. TNF-alpha also inhibited the ENaC function as indicated by the reduction of amiloride-sensitive current (control 4.4, TNF-alpha 1.9 microA/cm(2)). These data suggest that TNF-alpha may affect the pathophysiology of acute lung injury and pulmonary edema through the inhibition of alveolar liquid clearance and sodium transport.

One of the major challenges in the treatment of solid cancers by allogenic hematopoietic stem cell transfer (alloHSCT) is the specific enhancement of antitumor immunity. Interferon (IFN) is a cytokine with pleiotropic biological functions including an immunomoduration, and our preclinical studies have shown that an intratumoral IFN-alpha gene transfer induced strong local tumor control and systemic tumor-specific immunity. In the present study, we examined whether the IFN-alpha gene transfer could enhance recognition of tumor-associated antigens by donor T cells and augment the antitumor activity of alloHSCT. First, when a mouse IFN-alpha adenovirus vector (Ad-mIFN) was injected into subcutaneous xenografts of syngeneic renal and colon cancer cells, tumor growth was significantly suppressed in a dose-dependent manner. A significant tumor cell death and infiltration of immune cells was recognized in the Ad-mIFN-injected tumors, and the dendritic cells isolated from the tumors showed a strong Th1-oriented response. The antitumor effect of Ad-mIFN was then examined in a murine model of minor histocompatibility antigen-mismatched alloHSCT. The intratumoral IFN-alpha gene transfer caused significant tumor suppression in the alloHSCT recipients, and this suppression was evident not only in the gene-transduced tumors but also in simultaneously inoculated distant tumors which did not receive the vector injection. A cytotoxicity assay showed specific tumor cell lysis by donor T cells responding to IFN-alpha. Graft-versus-host disease was not exacerbated serologically or clinically in the mice treated with IFN-alpha. This combination strategy deserves evaluation in future clinical trials for human solid cancers.

A 48-year-old woman with small-cell lung cancer received combined chemotherapy consisting of cisplatin (CDDP) and etoposide (Vp-16). Although the gustatory threshold in the glossopharyngeal nerve area was normal (14 dB) before chemotherapy, it rose to 22 dB on day 8 of chemotherapy, and it could not be measured, because of severe gustatory disorder, from day 15 to day 29. In the chorda tympani nerve area, the threshold was normal until day 15, but it could not be measured on day 29. This gustatory disorder continued for 2 more months, until the time of the patient's discharge. Although gustatory disorder caused by anticancer drugs has been reported as a rare side effect, this may be because it has been reported as appetite loss, and it may happen more frequently than reported cases would suggest. As gustatory disorder reduces the patient's quality of life, the presence of this side effect should be given more serious consideration.

Amiloride-sensitive sodium channel (ENaC) plays an important role in recovery from pulmonary edema. Recently, it has been shown that an activation of protein kinase C (PKC) could affect the mRNA expression of ENaC in rat parotid gland cells and A6 distal nephron epithelial cells. To determine whether an activation of PKC would regulate the mRNA expression or the function of ENaC, we stimulated rat alveolar type II epithelial cells with phorbol 12-myristate 13-acetate (PMA), a potent PKC activator, at a concentration of 100 nM. The mRNA expression of alpha-, beta-, and gamma-ENaC subunits and amiloride-sensitive current were measured. PMA inhibited the mRNA expression of all 3 ENaC subunits (alpha-ENaC: 56.0% +/- 12.1%; beta-ENaC: 62.6% +/- 15.9%; gamma-ENaC: 68.5% +/- 10.6%, respectively) and amiloride-sensitive current (control = 7.0 +/- 1.5 microA/cm(2); PMA = 1.7 +/- 0.9 microA/cm(2)) significantly at 24 hours. On the other hand, 4alpha-phorbol didecanoate 4alpha-PDD, inactive form of PMA, had no inhibitory effect on alpha- and gamma-ENaC expression or amiloride-sensitive current. However, no significant difference was seen in beta-ENaC expression between PMA and 4alpha-PDD. GF 109203X, a wide-range PKC inhibitor, blocked the inhibitory effect of PMA on all ENaC subunits mRNA expression. These results suggest that an activation of PKC may play an important role in the regulation of ENaC mRNA expression and function.

Patients with bilateral hippocampal atrophy (BHA) in a subgroup suffering from mesial temporal lobe epilepsy represent a therapeutic challenge. We achieved successful surgical treatment in a case with BHA and false lateralized ictal onset on video-scalp electroencephalogram (EEG). A 27-year-old male patient with seizures since the age of 15 years showed current seizures consisting of an epigastric aura, a feeling of difficulty in breathing and oroalimentary automatism, which were frequently followed by secondary generalization with right-arm tonic extension. MRI showed BHA with hyperintensity on FLAIR and a slightly smaller volume in the left hippocampus on volumetry. Ictal EEG started from the left anterior temporal and subtemporal regions, spreading to the right anterior to middle temporal region. Interictal EEG was not lateralized, and showed independent spikes in the bilateral anterior temporal and subtemporal regions. The patient underwent chronic intracranial EEG-monitoring, revealing that the seizure onset originated from the right hippocampus with a rapid spread to the hippocampus and lateral temporal cortex on the left side. We performed a right anterior temporal lobectomy with amygdalohippocampectomy. Histological diagnosis was classic hippocampal sclerosis. The patient has since been seizure-free for 4 years. In this case, false lateralization may have been caused by an atypical seizure-propagating route to the contralateral temporal region via the dorsal hippocampal commissure instead of the usual pathway to the ipsilateral temporal neocortex. The technique of bilateral intracranial EEG-monitoring is advantageous to lateralize the actual side, particularly in BHA patients even with clearly and falsely lateralized ictal onset on scalp-EEG.

A 28-year-old male who presented a relapse of intractable epilepsy consisting of complex partial seizures with occasional secondary generalizations at the age of 26, had undergone removal of a left mesial temporal lobe tumor at another hospital at 18 years old. Pathological examination at that time revealed a low-grade astrocytoma, and the tumor was further treated by complementary adjuvant irradiation therapy. Magnetic resonance imaging (MRI) findings on admission portrayed a post-operative cavity anterior to the atrophied hippocampus on the left side with hyperintense in fluid-attenuated inversion recovery (FLAIR) images. There were no enhanced lesions in T1-weighted gadolinium images. As it was diagnosed as left mesial temporal lobe epilepsy with preoperative evaluations, the patient underwent left anterior temporal lobe resection (TLR). Intraoperative findings revealed that a small lump of grey tissue was attached to the anteromesial side of the sclerotic hippocampus. We surgically removed this and the tissue was a pilocytic astrocytoma. The patient has since remained seizure-free for 2.5 years. Seizure outcomes at postoperative 1-2 years are highly predictive of long-term outcomes after TLR for temporal lobe epilepsy (TLE). Late-seizure recurrence (postoperative 2 years) with an initially successful outcome rarely occurs in TLR patients. This case report suggests that recurrence of even benign pilocytic astrocytomas may occur when seizure recurs in long-term follow-up.

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional protein that was first identified in brain astrocytes and that has subsequently been shown to be expressed in different tissues. Despite its many important roles, the clinical significance of PEA-15 expression levels in astrocytic tumors has yet to be properly defined. We studied the PEA-15 expression pattern of 65 patients [diagnosed according to World Health Organization (WHO) criteria] with diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV). PEA-15 expression levels were immunohistochemically measured and categorized as no, low, or high expression. All tumors expressed PEA-15 in our study. Twenty-three (35.4%) and 42 (64.6%) tumors expressed low and high PEA-15 levels, respectively. In grade II astrocytoma (diffuse astrocytoma) and grade III astrocytoma (anaplastic astrocytoma), 100% and 88.9% of patients expressed high PEA-15 levels, respectively, while a smaller number (50%) of patients with grade IV astrocytoma (glioblastoma) expressed high PEA-15 levels. PEA-15 expression level was inversely associated with WHO grade (P = 0.0006). Next, we evaluated prognosis and PEA-15 expression levels in 43 patients with high-grade astrocytomas based on the following parameters: age, gender, WHO grade, surgical resection extent, MIB-1 labeling index (LI), and PEA-15 expression level. Multivariable analyses revealed that high PEA-15 expression level displayed a significant correlation with longer overall survival (OS) in high-grade astrocytomas (P = 0.0024). Patients with total resection survived significantly longer (P = 0.0044) than those with lower resection extent, while patients with MIB-1 labeling index a parts per thousand currency sign25% indicated significant (P = 0.0434) correlation with OS as well. In conclusion, PEA-15 expression level was inversely associated with WHO grade and may serve as an important prognostic factor for high-grade astrocytomas.

A conditionally replicative adenovirus is a novel anticancer agent designed to replicate selectively in tumor cells. However, a leak of the virus into systemic circulation from the tumors often causes ectopic infection of various organs. Therefore, suppression of naive viral tropism and addition of tumor-targeting potential are necessary to secure patient safety and increase the therapeutic effect of an oncolytic adenovirus in the clinical setting. We have recently developed a direct selection method of targeted vector from a random peptide library displayed on an adenoviral fiber knob to overcome the limitation that many cell type-specific ligands for targeted adenovirus vectors are not known. Here we examined whether the addition of a tumor-targeting ligand to a replication-competent adenovirus ablated for naive tropism enhances its therapeutic index. First, a peptide-display adenovirus library was screened on a pancreatic cancer cell line (AsPC-1), and particular peptide sequences were selected. The replication-competent adenovirus displaying the selected ligand (AdDeltaCAR-SYE) showed higher oncolytic potency in several other pancreatic cancer cell lines as well as AsPC-1 compared with the untargeted adenovirus (AdDeltaCAR). An intratumoral injection of AdDeltaCAR-SYE significantly suppressed the growth of AsPC-1 subcutaneous tumors, and an analysis of adenovirus titer in the tumors revealed an effective replication of the virus in the tumors. Ectopic liver gene transduction following the intratumoral injection of AdDeltaCAR-SYE was not increased compared with the AdDeltaCAR. The results showed that a tumor-targeting strategy using an adenovirus library is promising for optimizing the safety and efficacy of oncolytic adenovirus therapy.

Purpose: In autologous hematopoietic stem cell transplantation (HSCT), lymphopenia-induced homeostatic proliferation of T cells is driven by the recognition of self-antigens, and there is an opportunity to skew the T-cell repertoire during the T-cell recovery by engaging tumor-associated antigens, leading to a break of tolerance against tumors. However, the homeostatic proliferation–driven antitumor responses seem to decline rapidly in association with tumor growth. We hypothesized that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain homeostatic proliferation–induced antitumor immunity.Experimental Design: The antitumor effect of allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the immune reconstitution after syngeneic HSCT.Results: Syngeneic HSCT showed significant tumor growth inhibition of syngeneic colon cancer cells within a period of 30 days; however, the tumor then resumed rapid growth and the survival of the mice was not prolonged. In contrast, when the alloMHC plasmid was intratumorally injected at the early phase after syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities, whereas no survival advantage was recognized in recipient mice injected with a control plasmid. This tumor suppression was evident even in the other tumors that were not injected with the alloMHC plasmid. The antitumor response was characterized by the development of tumor-specific T cell– and natural killer cell–mediated cytotoxicities.Conclusion: The results suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer with an autologous HSCT for the treatment of solid cancers.

In this paper, we describe on a method for a three dimensional measurement of omni-directional space of camera view, using a fisheye stereo vision. In the method, the correction image is made from fisheye image. Three dimensional data of a moving object is calculated, using a parallax detected by template matching in the correction image. An ellipse as a geometrical model is calculated, using a plane coordinate on the object in real space. And a volume of the object is detected using the detected height and the ellipse. In the paper, composition of an experimental system and the measurement method are explained, and the experimental result is shown.

Background Direct revascularization through a superficial temporal artery-middle cerebral artery (STA-MCA) bypass is often performed to prevent ischemic or hemorrhagic attack in patients with moyamoya disease. This is the first reported case of aneurysm formation and rupture due to an STA-MCA bypass in a patient with moyamoya disease. Case Description A 52-year-old man who had undergone bilateral STA-MCA bypass for caudate hemorrhage due to moyamoya disease 20 years previously suffered from sudden-onset unconsciousness. Computed tomography revealed a massive intracerebral hematoma (ICH) in the left frontoparietal region. Angiography showed good patency of the anastomoses and stage IV moyamoya disease. However, no other abnormality was found. Emergency evacuation of the hematoma was performed. The patient's postoperative course was uneventful, but consciousness disturbance of sudden onset occurred 1 month later. Computed tomography showed a hematoma in the lateral ventricle and acute hydrocephalus. Repeat angiography revealed an aneurysm on the left side of the anastomosis. Bilateral ventricle drainage tubes were inserted, and the aneurysm was clipped. A ventriculoperitoneal shunt was later performed. Conclusion In patients with moyamoya disease who have undergone extracranial-intracranial bypass surgery, progressive hemodynamic stress may cause the formation of de novo aneurysms after a postoperative period of several decades. Imaging examinations should therefore be performed periodically for follow-up, and a de novo aneurysm should be suspected in a patient who has an unusual ICH.

A 55-year-old male was admitted to our hospital because of confusion and mild weakness of his left arm and leg. His condition had taken a gradual turn for the worse for several months. Computed tomography (CT) demonstrated a mixed density mass with multiple cysts and massive perifocal edema. Magnetic resonance imaging (MRI) demonstrated an irregular-shaped mass with multiple cysts sized 6 x 4 x 6 cm in the temporal lobe, which manifested mixed signal intensity on both the T1 weighted image and the T2 weighted image. MRI also revealed massive perifocal edema and marked midline shift. Gd-DTPA study showed ring-like enhancement. Angiography showed no tumor stain and a suppressed right posterior cerebral artery. A right extended temporo-occipital craniotomy was performed to extirpate the abscess subtotally. The histological examination showed brain abscess and Gram stain of the pus revealed the presence of gram-positive bacilli. The gram-positive bacillus, Corynebacterium only was subsequently cultured from the pus. After the operation his hemiparesis seemed to disappear. In spite of the treatment with multiple intravenous antibiotics, his hemiparesis worsened again. CT and MRI demonstrated recurrence of the brain abscess in the occipital lobe and marked perifocal edema. The second operation was performed and removed all the infected brain tissue with abscess. After the second operation, otorhinological and cardiovascular examinations were carried out, but no causal disease was found. Immunoelectrophoresis (total protein 12.2 g/d/) revealed the peak of M protein. Bone marrow revealed dysplasia of the plasma cell and he was diagnosed as having multiple myeloma that had made him an immunocompromised host.

A 52-year-old man was admitted to our hospital because of fever and dyspnea. Chest X-ray film showed infiltrative shadows in the right lower lung fields and serum creatinine was 6.7 mg/dl. The patient was diagnosed as pneumonia complicated with acute renal failure. He was treated with antimicrobial therapy. However he developed respiratory failure and exhibited mental confusion. Legionnaires' disease was suspected, because pneumonia was found to be associated with multiple organ dysfunction. We started treatment with intravenous administration of minocycline and continuous hemodiafiltration and his condition had been rapidly improved. We diagnosed this case as legionnaires' disease due to the positive of urinary Legionella pneumophila serogroup 1 antigen. Since the cases of legionnaires' disease with acute renal failure are serious, prompt diagnosis and adequate treatment are essential.

A 68-year-old man was admitted to our hospital because of hemoptysis in September 1999. Chest CT scans showed a nodular shadow with infiltration in the right S 7. Bronchial arteriography showed vascularization in the right S 7, and bronchial artery embolization was performed. However, in April and October 2000 hemoptysis recurred, and bronchial arteriography showed recurrence of vascularization in the same area, so embolization was performed again. Then, the patient was admitted in March 2001 because of recurrent hemoptysis. CT scans showed growth of the nodular shadow. Right lower lobectomy was performed, and the microscopic findings in the tissue from the resected lobe showed branching filamentous bacteria, and pulmonary actinomycosis was diagnosed. We concluded that pulmonary actinomycosis should be considered in the differential diagnosis of nodular shadows with recurrent hemoptysis.

A 63-year-old male was admitted to our hospital, complaining of a scalp mass located at the frontoparietal area of his head. He noticed that it had been growing for 2 months. The mass was elastic hard and non-moving. Computed tomography demonstrated a subcutaneous mass with low density and which was enhanced homogeneously. The skull just below the mass was slightly destroyed, but the structure remained. Magnetic resonance imaging (MRI) demonstrated a mass with low signal intensity on both the T1 weighted image and the T2 weighted image. Gd-DTPA study showed homogeneous enhancement and showed also that the dura just below the mass was enhanced. At this point we couldn't diagnose it confidently, but suspected this lesion to be a malignant lymphoma. We made a general examination, but no other lesion was found. A biopsy of the subcutaneous mass was performed under local anesthesia. The histological diagnosis was large-cell type B-Cell lymphoma. The tumor was treated with chemotherapy, CHOP (cyclophosphamid, doxorubicin, vincristin predonisolone). It responded to this chemotherapy and disappeared. We treated this lesion without radiation therapy. We report a case of subcutaneous malignant lymphoma treated successfully with a minimum invasive method.

Pleural fluid rarely occurs in patients with progressive systemic sclerosis (PSS) or polymyositis (PM) with no lesions in the pulmonary area. Pleural fluids in patients with autoimmune diseases are mostly dominated by monocytes and lymphocytes but very rarely contain increased eosinophils. We report a 55-year-old male with PSS-PM overlap syndrome and eosinophilic pleural effusion. Air invasion into the pleural cavity and the antituberculous therapy could be ruled out as causes for the patient's eosinophilic pleural effusion, because the differential eosinophil count was already as high as 19% from the first thoracentesis before the start of antituberculous therapy. Infections and malignant tumor also were unlikely causes based upon the negative pleural fluid results and the negative pleural biopsy findings, except for nonspecific inflammation. After the administration of corticosteroid, the pleural effusion decreased promptly, with normalization of serum creatine phosphokinase and C-reactive protein concentrations.

A 48-year-old man was diagnosed with primary alveolar proteinosis (PAP). Whole lung lavage was performed for treatment, and the opacity on his chest X-ray completely disappeared. The value of cytokeratin 19 fragment (CYFRA) in the serum was high at the beginning, decreased after lung lavage, and became elevated again when the disease recurred 7 months later. As PAP is thought to be a problem of surfactant secreted from type II pneumocytes, and a cytokeratin is present in the alveolar epithelial tissue, the value of serum CYFRA might be related to the severity of PAP.

Recombinant adenovirus vectors have been widely used for gene delivery to a range of cell types and employed in a number of gene therapy approaches. However, a selective delivery of a therapeutic gene to target cells by adenovirus vectors is precluded by the widespread distribution of the primary cellular receptors for adenoviruses. Recently, retargeting adenovirus vectors has been achieved by direct genetic modifications of the capsid proteins: targeting ligands can be incorporated into the C-terminal and HI-loop of fiber proteins ablated for native tropism through loss of binding with CAR and av integrins, and these vectors provide an important platform for evaluating the targeting potential of selected peptide ligands. However, cell-type specific lligand-receptor systems for targeted adenovirus vectors are generally unknown, which impedes the wider application of fiber-modified adenovirus vectors for targeted therapies. Moreover, because the insertion of a pre-selected peptide into a fiber knob often fails to generate an adenovirus vector as shown in this study, the selection of targeting peptides is highly useful in the context of the adenoviral capsid. We reported previously a simple and efficient method for constructing an adenovirus cDNA expression library by in vitro Cre-loxP recombination (K. Hatanaka, et al. Mol Ther 8;158, 2003). Based on that technology, here we developed a novel system for adenoviral libraries which display a wide variety of peptides on the HI-loop of the fiber knob. A plasmid-based library containing a GFP clone at an abundance of 0.01% was readily converted to the adenovirus library in a convenient 60-mm dish scale, suggesting that the complexity of the virus library could be more than 1 |[times]| 104 per a 60-mm dish by the present method. As proof-of-concept, we screened the 2 |[times]| 105 complexity level of adenovirus display library on a human gliomacell line and observed selection of a particular peptide sequence. The gene transduction efficiency of a targeted vector carrying the peptide was 4- to 5-fold higher than that of an untargeted adenovirus in the glioma cell line but not in other cell lines. A substantial competitive inhibition by the cognate peptide but not by a control unrelated peptide was observed, confirming that the enhanced transduction of the targeted vector in the cells is mediated by the insertion of the selected peptide. Our system may allow the selection of specific targeted vectors to any given cell type of interest, and may have broad implications for the development of targeted therapies.

BackgroundThe efficacy of montelukast, a specific cysteinyl leukotriene receptor antagonist, in preventing recurrent asthma attacks was evaluated for post-emergency management of acute asthma exacerbation.MethodsTwenty-two patients with a history of chronic asthma whose symptoms were responsive to an inhaled β-adrenergic receptor agonist in an emergency room setting, were randomized into two groups, those with and those without montelukast (n = 11 for each group). Patients in the montelukast group received an oral dose of 10 mg montelukast before leaving the emergency room following rescue treatment with an inhaled β-adrenergic receptor agonist. Patients in both groups were instructed to use an inhaled β-adrenergic receptor agonist for shortness of breath or dyspnea in post-emergency management. Additional β-adrenergic receptor agonist use, subjective asthma symptoms, sleep impairment, additional emergency visits and/or hospitalization were monitored for 24 hours following the emergency room visit.ResultsIn the montelukast group, the need for a rescue β-adrenergic receptor agonist was significantly decreased; 54.5% of patients in the montelukast group required use of β-adrenergic receptor agonist compared with 100% in the non-montelukast group (P < 0.05). The average number of uses of a β-adrenergic receptor agonist was 2.67 ± 3.58 times/ 24 h in the montelukast group compared with 11.95 ± 3.60 times/24 h in the non-montelukast group (P < 0.01). The average subjective asthma symptom scores were significantly decreased in the montelukast group, whereas no score change occurred in the non-montelukast group. The sleep impairment score was significantly lower in the montelukast group compared with that in the non-montelukast group (P < 0.05). No patients in either group had an emergency visit or hospitalization during this period.ConclusionsThe results demonstrate that montelukast can prevent recurrent asthma exacerbations in the home environment.