Biomedical subjects
Publications and source records attributed to Takashi Kato.
A triphenylphosphine oxide (TPPO) compound bearing 3,4,5-tridodecyloxybenzyloxy moieties exhibits a columnar liquid crystalline phase, and by changing its self-assembled structure, is responsive to alkaline metal cations due to cation-phosphine oxide interactions.
The source of a fever of unknown origin (FUO) and watery diarrhea in a 63-yr-old female with a history of disturbance of consciousness due to moyamoya disease was examined. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), colonoscopy, blood analysis, and determination of cytomegalovirus (CMV) antigenemia were performed. FDG was found to be accumulated in the wall of a dilated colon, and extended from the transverse to sigmoid colon. Colonoscopy revealed edematous, inflammatory, and punched out lesions in accordance with the areas of abnormal FDG uptake. A biopsy specimen showed the antibody of CMV in the colonic mucosa, and CMV antigenemia was detected by an immunohistochemical assay using a monoclonal antibody for CMV pp65 antigen. From these findings, we strongly suspected CMV enteritis.
PURPOSE: We investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver. METHODS: Five patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 +/- 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated. RESULTS: The portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH(2)O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH(2)O to 258 mmH(2)O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl. CONCLUSIONS: We recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.
A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high fever triggered by administration of an influenza vaccine after a 4-month-long effective treatment course with the TNF-alpha inhibitor etanercept. Influenza vaccine had been previously administrated safely to the patient before initiation of etanercept therapy. The fever occurred without other symptoms soon after vaccine administration, progressed to high fever 1 day later, and spontaneously resolved the second day. The clinical course appears to be compatible with drug fever closely associated with immediate hypersensitivity (in particular, late-phase type I allergic reaction), in which T helper (Th) 2 cells play a crucial role. Etanercept can strongly suppress Th1-mediated reactions; therefore, Th2 activity may be augmented by etanercept treatment in aspect of antagonism between Th1 and Th2 mechanisms. In RA patients who receive treatment with TNF-alpha inhibitor such as etanercept, activation of Th2-mediated immune responses such as immediate hypersensitivity may be a necessary side effect for those who receive vaccinations.
PURPOSE: The aim of this study was to examine abnormalities of the central nervous system in patients with chronic pain who were diagnosed with complex regional pain syndrome (CRPS). MATERIALS AND METHODS: Brain activity was assessed using (18)F-fluorodeoxyglucose positron emission tomography. The data collected from 18 patients were compared with data obtained from 13 normal age-matched controls. RESULTS: Our results showed that glucose metabolism was bilaterally increased in the secondary somatosensory cortex, mid-anterior cingulated cortex (ACC) or posterior cingulated cortex (PCC) (or both), parietal cortex, posterior parietal cortex (PPC), and cerebellum as well as in the right posterior insula and right thalamus in our patients. In contrast, glucose metabolism was reduced contralaterally in the dorsal prefrontal cortex and primary motor cortex. Glucose metabolism was bilaterally elevated in the mid-ACC/PCC and the PPC, which correlated with pain duration. CONCLUSION: These data suggested that glucose metabolism in the brains of patients with CRPS changes dramatically at each location. In particular, glucose metabolism was increased in the areas concerned with somatosensory perception, possibly due to continuous painful stimulation.
STUDY OBJECTIVES: We investigated pleural fluid penetration of carbapenem antibiotic agents [imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM)] using an experimental rabbit pleuritis model to clarify the usefulness of the carbapenem agents for the treatment of bacterial pleurisy or pyothorax. MEASUREMENTS AND RESULTS: Serum and pleural fluid specimens were serially collected at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min after antibiotic administration for measurement of antibiotic levels. We investigated each agent alone as well as drug solutions containing each agent and a dehydropeptidase-I-specific inhibitor, cilastatin (CS), to remove the influence of dehydropeptidase-I-related hydrolysis. Groups of animals (n=3) received each carbapenem agent with or without CS. Serum and pleural fluid antibiotic levels were measured by high-performance liquid chromatography (HPLC). Because Cmax is not useful for evaluating the antimicrobial effects of carbapenem antibiotic agents due to their dose-dependent antimicrobial activity, we also investigated the AUC, which is correlated with the total drug levels in vivo. Among the drug solutions containing CS, MEPM/CS had the highest pleural fluid AUC0-360 (1594.8+/-510.3 microg min/ml), and the highest pleural fluid AUC0-360/plasma AUC0-360 ratio (0.79+/-0.04). BIPM/CS had the highest plasma AUC0-360 (3040.1+/-1525.9 microg min/ml). In pleural fluid AUC0-360/plasma AUC0-360 ratio MEPM/CS was significantly higher than those for the remaining agents. In pleural fluid AUC0-360 and plasma AUC0-360 there were no significant differences among these mixed solutions. CONCLUSIONS: MEPM had the most favorable pleural fluid penetration. Pleural fluid penetration should be examined in infection models and in clinical trials.
OBJECTIVE: We have developed a new CT-guided technique using puncture site-down positioning during the biopsy. The goal of our study was to determine the efficacy and safety of this technique for biopsy of lung lesions compared with the standard technique. MATERIALS AND METHODS: Medical records of 236 patients who underwent CT-guided transthoracic needle biopsy were retrospectively evaluated. This study included 89 cases that were biopsied using the standard technique (group A) and 147 cases that were biopsied using the puncture site-down positioning technique (group B). A 20-gauge automated cutting needle without coaxial technique was used in all patients. Medical records were reviewed for lesion size and location, biopsy results, and complications. RESULTS: When using the standard technique, the sensitivity for malignant lesions was 96.1%; the sensitivity for benign lesions, 92.1%; and diagnostic accuracy, 94.4%. Thirty-seven patients (41.6%) had pneumothorax, with 16 (18.0%) requiring chest tube placement. When using the puncture site-down positioning technique, the sensitivity for malignant lesions was 95.4%; the sensitivity for benign lesions, 93.3%; and diagnostic accuracy, 94.6%. Nineteen patients (12.9%) had pneumothorax, with four (2.7%) requiring chest tube placement. Other complications were minimal. CONCLUSION: CT-guided transthoracic needle biopsy using the puncture site-down positioning technique is an effective and safe procedure with a high diagnostic accuracy and low complication rate. This new technique is especially useful in reducing the rate of pneumothorax.
Sandarac resin, a natural gum base, is described as "a substance composed mainly of sandaracopimaric acid obtained from the secretion of sandarac trees" in the List of Existing Food Additives in Japan. To evaluate its quality as a food additive, the main constituents in a sandarac resin product were investigated. Three constituents were isolated and identified as sandaracopimaric acid, sandaracopimarinol and 4-epidehydroabietic acid by MS and 2D-NMR. Quantification of the main constituent, sandaracopimaric acid, was performed by HPLC and its content in the product was determined to be 11.6%.
This report examines the clinical parameters and radiographic characteristics of two patients with Class III gingival recession who were treated with combined connective tissue grafting and root coverage with enamel matrix derivative. Both patients presented with multiple Class III recessions in the mandibular central incisors. Root coverage was achieved by connective tissue grafting in conjunction with the application of enamel matrix derivative. Soft tissue coverage of the root surfaces was achieved clinically, and radiographs showed improvement in the interproximal vertical bone defects.
UNLABELLED: The rupture of atherosclerotic vulnerable plaques and subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Because macrophage infiltration plays an essential role in plaque rupturing, pharmacologic therapy that reduces macrophage infiltration is required to stabilize the vulnerable plaques. The monitoring of therapeutic effect is important in assessing the therapeutic effects of drugs for individual patients. We previously reported that (18)F-FDG accumulates in macrophage-rich plaques. The present study was undertaken to investigate the usefulness of (18)F-FDG PET for monitoring therapies that target vascular inflammation. METHODS: Myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits were used in this study. The antioxidant probucol was included in the diet fed to 4 rabbits starting at 10 mo of age (probucol group). In a control study, 4 rabbits received standard rabbit chow (control group). (18)F-FDG PET experiments were performed on both groups before the study and at 1, 3, and 6 mo after treatment. After the last imaging session, the rabbits were sacrificed at 3 h after injection of (18)F-FDG, and the aortas were removed. The accumulated radioactivity was then measured, and the number of macrophages was determined by examination of stained sections. RESULTS: At the age of 10 mo, before the treatment, the aorta could be imaged by (18)F-FDG PET in all rabbits. The aorta could not be imaged after 6 mo of probucol treatment, whereas intense radioactivity was observed in the control rabbits throughout the investigation. The standardized uptake values (SUVs) of the aorta were decreased significantly in the probucol group after 3 mo of intervention as compared with the pretreatment period. The SUVs of the control group were increased gradually at 6 mo. Radioactivity in the aorta was significantly lower in the probucol group than that in the control group. Macrophages were already present at the beginning of the study, and probucol treatment for 6 mo resulted in a significant reduction of macrophage infiltration. CONCLUSION: (18)F-FDG PET was able to image the reduction of inflammation by probucol. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can stabilize vulnerable plaques. (18)F-FDG PET should be useful for evaluating the therapeutic effect of drugs clinically and for the development of new drugs that can reduce inflammation of vulnerable plaques.
In the 21st century, soft materials will become more important as functional materials because of their dynamic nature. Although soft materials are not as highly durable as hard materials, such as metals, ceramics, and engineering plastics, they can respond well to stimuli and the environment. The introduction of order into soft materials induces new dynamic functions. Liquid crystals are ordered soft materials consisting of self-organized molecules and can potentially be used as new functional materials for electron, ion, or molecular transporting, sensory, catalytic, optical, and bio-active materials. For this functionalization, unconventional materials design is required. Herein, we describe new approaches to the functionalization of liquid crystals and show how the design of liquid crystals formed by supramolecular assembly and nano-segregation leads to the formation of a variety of new self-organized functional materials.
Nanostructures can be used for the fabrication of highly functional materials transporting ions and charges. We demonstrate a new design strategy for polymeric higher ion-conductors. Phase-segregated layers of alternating mobile tetra(ethylene oxide)s (TEOs) and rigid aromatic cores where the TEO moieties are grafted from aromatic layers have been shown to be efficient to transport lithium triflate. Such segregated structures at the nanometer scale (nano-segregated structures) were prepared by in-situ photopolymerization of an aligned methacrylate liquid crystalline monomer comprising a terphenyl rigid rod mesogen having a TEO terminal chain. The ion-conductive TEO moiety remains in the highly mobile state even after polymerization, which is indicated by its low glass transition temperature (-45 degrees C). This nanostructured film exhibits an ionic conductivity parallel to the layer of 10(-3) S cm(-1) at room temperature. The highest ionic conductivity is in the level of 10(-2) S cm(-1) observed at 150 degrees C. The anisotropic ionic conductivities have been observed for the nano-segregated film.
New electroactive supramolecular fibers have been formed by self-assembly of the derivatives of tetrathiafulvalene (TTF) in liquid crystals. These derivatives are designed and prepared by introducing the TTF moiety to the scaffold derived from amino acids such as L-isoleucine whose derivatives function as organogelators. These TTF-based gelators form stable fibrous aggregates in liquid crystals. These fibers are the first example of hydrogen-bonded one-dimensional aggregates having electroactive moieties whose electrical conductivities were measured after doping. Their electronic states have also been characterized by spectroscopic methods. Unidirectionally aligned fibers are formed in the oriented liquid crystal solvents on the rubbed polyimide surface for further functionalization of the fibers.
A 24-year-old Japanese woman was admitted for investigation of recurrent spiking high fever associated with a macular eruption of the upper extremities associated with fever and polyarthralgia. These symptoms were self-limiting but recurrent and seemed to be consistent with a diagnosis of adult-onset Still's disease (AOSD). However, livedo reticularis was detected on the lower extremities, suggesting the presence of vasculitic disease rather than AOSD. Investigation did not reveal any evidence of visceral involvement. Skin biopsy of the affected lower extremity demonstrated a necrotizing vasculitis of small muscular artery and confirmed a diagnosis of cutaneous polyarteritis nodosa (PAN) rather than AOSD. Treatment with 30 mg of prednisolone daily improved the skin lesions and the recurrent spiking high fever and the arthralgia were resolved. PAN and AOSD are clinically similar, and discrimination may be sometimes difficult. The presence of livedo reticularis and the finding of a characteristic skin biopsy appearance may be diagnostically useful to distinguish PAN from AOSD. Indeed, the clinical features of cutaneous PAN may be more similar to AOSD than systemic PAN, and a skin biopsy may be necessary to distinguish cutaneous PAN from AOSD in some cases.
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the main causes of refractory infections that are often resistant to antimicrobial agents. In these cases, combination of agents with antimicrobial activity is being examined. However, few studies have investigated combined effects with antimicrobial agents including carbapenem and aminoglycosides. METHODS: We evaluated the effects of panipenem (PAPM) combined with 3 aminoglycosides, arbekacin, amikacin, and netilmicin, and vancomicin (VCM) with an agar dilution checkerboard technique and the fractional inhibitory concentration index against 47 strains of MRSA and 56 strains of P. aeruginosa. RESULTS: PAPM combined with VCM achieved a synergic effect against MRSA in 80.9%. PAPM combined with aminoglycosides showed only additive effects against MRSA and P. aeruginosa. When comparing the activity of Mueller-Hinton agar (MHA) medium with MHA medium diluted 40-fold (1/40 MHA) against P. aeruginosa, the mean minimum inhibitory concentration of PAPM was decreased to 1/16. CONCLUSIONS: Combination of PAPM and VCM is effective against MRSA. Combinations of PAPM and aminoglycosides showed additive effects against MRSA and P. aeruginosa.
The conditions under which the attractive electron-electron interactions are realized in the monocations of sigma-conjugated cyanodienes such as C(6)N(4)H(4), C(8)N(6)H(4), and C(10)N(8)H(4) and of pi-conjugated acenes are discussed. The total electron-phonon coupling constants for the monocations l(HOMO) of cyanodienes are much larger than those for the monocations of acenes. The strong sigma orbital interactions between two neighboring atoms in the highest occupied molecular orbitals (HOMO) of sigma-conjugated cyanodienes are the main reason for the calculated results. Furthermore, we discuss how the conditions under which the monocation crystals become good conductor are related to the molecular size. Both the l(HOMO) values and the reorganization energies between the neutral molecules and the monocations decrease with an increase in molecular size in cyanodienes. The calculated results for the sigma-conjugated cyanodienes are compared with those for the pi-conjugated acenes in order to investigate how the CH-N substitutions in cyanodienes are closely related to the l(HOMO) values and the reorganization energies. Both the l(HOMO) and the reorganization energies in the positively charged sigma-conjugated cyanodienes are much larger than those in the positively charged pi-conjugated acenes. This means that in order to become good conductors, the positively charged sigma-conjugated cyanodienes need larger overlap integral between two adjacent molecules than the positively charged pi-conjugated acenes. On the other hand, since the l(HOMO) values for cyanodienes are much larger than those for acenes, the condition of attractive electron-electron interactions is more easily to be realized in the monocations of cyanodienes than in the monocations of acenes. It is suggested that the positively charged sigma-conjugated cyanodienes cannot easily become good conductors, but the conditions under which the electron-electron interactions become attractive are realized more easily in the positively charged sigma-conjugated cyanodienes than in the positively charged pi-conjugated acenes.
Pruritus is a common, distressing and difficult to manage complication of many autoimmune diseases. A suitable animal model of autoimmune disease associated pruritus would contribute to a better understanding of the pathophysiology of this symptom and lead to the development of safe and effective antipruritic agents. We noticed spontaneous scratching behavior in aged MRL/lpr mice, a model of autoimmune disease. This scratching behavior was observed in a specific pathogen-free environment and was more frequent in female mice. In contrast to animal models of dermatitis; NC/Nga mice, the serum IgE and IgG1 levels in MRL/lpr mice were not elevated. These features indicate that this scratching behavior is similar to human autoimmune disease associated pruritus. The antipruritic effects of an antihistamine (chlorpheniramine), an opioid receptor antagonist (naltrexone), and a novel kappa-opioid receptor agonist (nalfurafine hydrochloride [TRK-820]) were evaluated. The frequency of scratching was not reduced by oral administration of chlorpheniramine, suggesting that the behavior is antihistamine-resistant. The oral administration of nalfurafine and subcutaneously administered naltrexone inhibited the scratching behavior without causing gross behavioral changes. In conclusion, MRL/lpr mice scratching behavior is a suitable model of pruritus that occurs in autoimmune diseases, and nalfurafine was shown to be efficacious against this behavior suggesting that it may be beneficial in patients with autoimmune disease associated pruritus.
Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.