Liver toxicity of intravenous heparin treatment in patients with acute ischemic stroke.

Objective: Serum alanine aminotransferase (ALT), which is an indicator of liver dysfunction, may increase during treatment in patients in the acute phase of stroke. However, the cause of the ALT elevation is unclear, as multiple medications are often being used. We investigated the relationship between medications used in acute ischemic stroke, including cerebral infarction and transient ischemic attack, and ALT elevation.

HiSAT: A Novel Method for the Rapid Diagnosis of Allergy.

To identify causative substances for allergies to drugs or foods, the lymphocyte transformation test (LTT) is currently widely used as in vitro test, but its accuracy is not satisfactory. We have developed a novel method designated high-sensitivity allergy test (HiSAT) for determining allergy expression by measuring cell kinetics, using the chemotactic cells from non-allergic volunteers against a gradient field of cytokines released from immune cells when allergy develops. HiSAT requires a very small sample of 5 µL or less, and is applicable to three types of tests, depending on the situation in clinical practice: (i) diagnosis of the allergic expression, (ii) identification of the causative drug, and, in principle, (iii) pre-inspection.

Novel method to analyze cell kinetics for the rapid diagnosis and determination of the causative agent in allergy.

Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively).

How to introduce a rotigotine patch to Parkinson's disease patients taking oral dopamine agonists.

Objective: Ways of introducing a rotigotine patch to Parkinson disease (PD) patients include initial induction for dopamine agonist (DA)-free patients and overnight switch (OS), cross-titration (CT), and add-on (AO) for patients already taking oral DAs. We investigated whether or not the introductions method affects the continuation rate of rotigotine patch.

Methods: The subjects were 188 PD patients who started using a rotigotine patch at the Department of Neurology, Fukuoka University Hospital.

Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies.

Background: Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting.

[Efficacy of Topical Agents for Symptomatic Treatment of Rotigotine Patch-Induced Skin Disorders].

Since the effect of a percutaneous absorption-type dopamine agonist (DA) preparation, rotigotine patch, stably persists by once-a-day application, this dosage form is appropriate for Parkinson's disease patients showing levodopa induced wearing off phenomenon. On the other hand, skin disorders, mainly application site reaction, are characteristic problems associated with use of the patch. In this study, to clarify the influence of a topical agent used to prevent or treat rotigotine patch-induced skin disorder on continuation of the patch application, patients who started rotigotine patch application at our hospital were retrospectively surveyed.

Enhancement of antitumor activity by using a fully human gene encoding a single-chain fragmented antibody specific for carcinoembryonic antigen.

Human leukocyte antigen and/or costimulatory molecules are frequently lacking in metastatic tumor cells, and thus tumor cells are able to escape from the immune system. Although lymphocytes with a chimeric antigen receptor (CAR) is a promising approach for overcoming this challenge in cancer immunotherapy, administration of modified T cells alone often demonstrates little efficacy in patients. Therefore, in order to enhance the antitumor activity of immune cells in the cancer microenvironment, we used lymphocytes expressing CAR in combination with a fusion protein of IL-2 that contained the single-chain fragmented antibody (scFv) specific for the carcinoembryonic antigen.

[Influence of Memantine on Continuous Treatment with Rivastigmine Patches-Retrospective Study Using the Logistic Regression Analysis].

Rivastigmine patches exhibit stable effects when attached once a day, and may reduce Alzheimer's disease (AD) patient's or caregiver's burden. On the other hand, it was reported that adverse events, such as dermal disorder, frequently appeared after the start of rivastigmine administration. We retrospectively investigated medical records in 120 patients with moderate or mild AD in whom rivastigmine administration was started in the Department of Neurology, Fukuoka University Hospital between July 2011 and June 2014 (43 males, 77 females, mean age: 76.

[Continued Use of Rotigotine Transdermal Patches for Parkinson Disease].

Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy.

Corrigendum to "Molecular Characterization of a Fully Human Chimeric T-Cell Antigen Receptor for Tumor-Associated Antigen EpCAM".

[This corrects the article DOI: 10.1155/2012/853879.].

Potent and specific antitumor effect of CEA-targeted photoimmunotherapy.

Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor-targeted PDT using a near-infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab-assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo.

[Establishment of an educational program concerning adverse drug reaction reporting-system in long-term practical training at a hospital].

The model core curriculum for pharmaceutical education specifies the specific behavioral objectives (SBOs) concerning adverse drug reactions, which aims to train pharmacy students to manage adverse drug reactions. Fukuoka University Hospital has developed a problem-based learning (PBL) program concerning adverse drug reactions as long-term practical training to collect adverse event information, identify adverse effects, and acquire management skills. Students' level of satisfaction with the program was high (approximately 90%), and the mean self-evaluation score for the SBOs concerning adverse reaction was 4.

Tumor growth inhibition by sonodynamic therapy using a novel sonosensitizer.

Sonodynamic therapy (SDT) with low-intensity ultrasound combined with a sonosensitizer may be a promising approach to cancer therapy. Use of ultrasound has the advantage of being noninvasive, with deep-penetration properties, and convenient because of the low or no sensitivity of sonosensitizers to light. In this study, SDT with a novel sonosensitizer (a porphyrin derivative) was evaluated in vitro and in vivo.

Molecular characterization of a fully human chimeric T-cell antigen receptor for tumor-associated antigen EpCAM.

The transduction of T cells to express chimeric T-cell antigen receptor (CAR) is an attractive strategy for adaptive immunotherapy for cancer, because the CAR can redirect the recognition specificity of T cells to tumor-associated antigens (TAAs) on the surface of target cells, thereby avoiding the limitations of HLA restriction. However, there are considerable problems with the clinical application of CAR, mostly due to its xenogeneic components, which could be immunogenic in humans. Moreover, while extensive studies on the CARs have been performed, the detailed molecular mechanisms underlying the activation of CAR-grafted T cells remain unclear.

Enhancement of the antitumor effect on combination therapy of an anticancer drug and its antibody against carcinoembryonic antigen.

Background: Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated.

Sonodynamic therapy with 5-aminolevulinic acid and focused ultrasound for deep-seated intracranial glioma in rat.

Background: 5-Aminolevulinic acid (5-ALA) has already been applied clinically as a photosensitizer. In this study, sonodynamically induced selective antitumour effect of 5-ALA for deep-seated lesions was evaluated.

Materials And Methods: First, normal rat brains were sonicated via a transducer placed on the dural surface to confirm safe acoustic conditions for normal rat brains.

Sonodynamic cancer therapy: a non-invasive and repeatable approach using low-intensity ultrasound with a sonosensitizer.

The low-intensity ultrasound that is used in clinical diagnoses, such as abdomen echo inspection, is a non-invasive treatment, and penetrates deeper into the body than light. Recently, sonodynamic therapy (SDT), which uses low-intensity ultrasound together with a sonosensitizer, has been developed for cancer therapy in applying such properties of ultrasound. So far, most sonosensitizers that have been developed are sensitive to light as well as ultrasound, implying that the shortcomings of photosensitizers used during photodynamic therapy, such as skin sensitivity, still need to be overcome in SDT.

Measurement and assessment of cytomegalovirus of immunoglobulin (Ig) g titer in preparations.

Cytomegalovirus (CMV) remains the most important pathogen following solid organ transplantation and is the major cause of recipient morbidity and mortality during the first 6 months posttransplantation. To prevent CMV infection and/or to prevent symptomatic CMV disease, immunoglobulin (Ig) G including hyperimmune CMV IgG are used alone or in combination with antiviral medications. The CMV IgG titer, however, has a wide range and frequently depends on the company supplying the Ig preparation even if the preparations come from the plasma pool of a national blood donation agency.

[Establishment of a system for early exposure provided by new pharmacists in a hospital].

It is very important for students to undergo early exposure in 6-year pharmaceutical education; through this experience they will understand roles of pharmacists, map out their future career, and increase their motivation for learning. Therefore we had newly recruited pharmacists provide an early exposure program in a hospital. According to the results of a questionnaire survey involving students, educational staff of the Faculty of Pharmaceutical Sciences and the new pharmacists, 99% of the students were satisfied with the program, and their motivation for learning was enhanced.

PPARalpha ligand WY14643 reduced acute rejection after rat lung transplantation with the upregulation of IL-4, IL-10 and TGFbeta mRNA expression.

Background: The peroxisome proliferators-activated receptor-alpha (PPARalpha) is important in lipid metabolism and regulation of inflammation. Recent studies have demonstrated the immunoregulatory effects of PPARalpha. This investigated the immunosuppressive effects of PPARalpha using its ligand, WY14643, on acute lung allograft rejection in a rat model and its mechanism of action.

Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer.

Background: The molecular and morphological alterations of the tight junctions in colorectal cancer (CRC) are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins (TJPs), was investigated in the tumorigenesis of CRC.

Patients And Methods: Adenocarcinoma tissue and paired normal mucosa specimens were resected from surgical specimens of CRC patients and analyzed to determine whether the expression of CL-1 correlated with the clinicopathological factors and to determine the role of CL-1 in the alteration of tight junctions during tumorigenesis.

Recombinant human monoclonal igA antibody against CEA to recruit neutrophils to CEA-expressing cells.

IgA is able to trigger antibody-dependent cellular cytotoxicity (ADCC) by recruiting neutrophils expressing the Fc receptor for the CHalpha chain. We herein describe the preparation of a human recombinant anti-CEA IgA antibody to kill carcinoembryonic antigen (CEA)-expressing tumor cells via ADCC by neutrophils. A single chain Fv (scFv) gene was constructed using a cDNA library of a hybridoma clone that produces a human anti-CEA monoclonal IgG4 (C2-45).

Association between the expression of chemokine receptors CCR7 and CXCR3, and lymph node metastatic potential in lung adenocarcinoma.

Chemokines and their receptors are essential for leukocyte trafficking, and are also involved in cancer metastasis to specific organs. Although the migration of tumor cells into the lymph nodes is an important aspect of cancer, the processes involved are poorly understood. Chemokine receptors CCR7 and CXCR3 have been shown to play an important role in tumor cell migration and lymph node metastasis.

Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer.

Background: To understand the molecular and morphological alterations in the tight junction in colorectal cancer (CRC) tissues, the expression of eight tight junction proteins in normal and cancer colorectal tissues were compared.

Patients And Methods: Adenocarcinoma tissues and paired normal mucosa were resected from surgical specimens of CRC patients. The expression of occludin, ZO-1, ZO-2, and claudin-1 -5 was analyzed at the mRNA level by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by immunohistochemistry.

Cancer-targeting gene therapy using tropism-modified adenovirus.

Gene therapy has the potential to provide highly selective, curative cancer treatments without inducing systemic toxicity. Adenoviral vectors have been extensively used for cancer gene therapy because of their relatively high efficacy of gene transfer. However, gene transduction to cancer cells is limited by the necessity of using adenoviral type 5 vectors.