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A precise understanding of the neural substrates underlying tactually-related cognitive impairments such as bilateral tactile agnosia, bilateral agraphesthesia, kinesthetic alexia and kinesthetic reading difficulty is currently incomplete. In particular, recent data have implicated a role for the lateral occipital tactile visual region, or LOtv, in tactile object naming (Amedi et al. Cerebral Cortex 2002). Thus, this study set out to examine the degree to which the LOtv may be involved in tactually-related cognitive impairments by examining two unique cases.To assess whether LOtv or the visual word form area (VWFA) is involved in tactually-related cognitive impairments, the average activation point of LOtv and that of VWFA were placed on the single-photon emission computed tomography (SPECT) cerebral blood flow images of two patients: one with bilateral associative tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading, and the other with kinesthetic reading difficulty.The average LOtv coordinate was involved in the area of hypoperfusion in both patients, whereas that of VWFA was not included in any of the hypoperfused areas.The results support the view that interruption of LOtv or disconnection to LOtv and to VWFA may cause these tactually-related cognitive impairments. Further, bilateral associative tactile agnosia and bilateral agraphesthesia are attributable toward the damage of the occipital lobe, whereas unilateral or predominantly one-sided associative tactile agnosia and agraphesthesia are attributable toward the damage of the parietal lobe.

We report a case of Campylobacter fetus (C. fetus) meningitis that manifested a chronic clinical course in an asplenic diabetic patient. The patient had eaten raw beef liver, and after 1 week, he suffered from headache and fever, with repeated remissions and deterioration. Four weeks after onset, neck stiffness was observed, and he was diagnosed with meningitis due to Campylobacter fetus. The cerebrospinal fluid (CSF) sample showed leukocytosis (3760/μl; neutrophils 91 %, lymphocytes 9 %). The infection responded to meropenem and ampicillin. A review of the literature between 1976 and 2013 revealed that C. fetus meningitis in adults is still a rare entity, and about one-third of case reports written in English are from Japan. We specifically reviewed the case reports of C. fetus meningitis in adults written in Japanese between 1979 and 2013 to examine the clinical features and influence of underlying disease, especially diabetes mellitus. Unexpectedly, most patients with C. fetus meningitis manifested a chronic clinical course, and CSF samples showed lymphocyte-predominant leukocytosis in at least 25 out of 43 cases. Antibiotic treatment, especially with carbapenem, was effective, and the overall prognosis of C. fetus meningitis was good, but 3 out of 43 patients had after effects. Two of the patients had diabetes mellitus as an underlying disease.

A 65-year-old woman developed progressive apraxic agraphia, characterized by poorly formed graphemes, a kanji (Japanese morphograms) recall impairment, relatively preserved oral spelling of kanji characters, and incorrect stroke sequences on writing accompanied by micrographia over a 3-year period. She also showed minor degrees of rigidity, limb-kinetic apraxia, and ideomotor apraxia of the left hand. Although asymmetric rigidity and limb-kinetic apraxia strongly suggested corticobasal degeneration, (11)C-Pittsburgh compound B positron emission tomography (PiB-PET) showed the predominantly right-sided accumulation of amyloid β in the cortices and striatum. (18)F-fluoro-deoxy-glucose PET and single photon emission computed tomography with a (99m)Tc-ethylcysteinate dimer (ECD-SPECT) also revealed predominantly right-sided hypometabolism and hypoperfusion in the primary sensorimotor cortex, posterior cingulate gyrus, temporoparietal cortices, frontal cortices, thalamus, and basal ganglia, a pattern characteristic of both corticobasal degeneration and Alzheimer's disease. The findings suggest that progressive apraxic agraphia with micrographia presenting as corticobasal syndrome can show an Alzheimer's disease pathology. It is also suggested that ideomotor apraxia of the left hand can occur without a callosal lesion, and is caused by hypometabolism or hypoperfusion in the right frontal and parietal cortices, as revealed by PET and SPECT.

Two patients with isolated thalamic agraphia are described. Both showed kanji (Japanese morphograms) agraphia due to impaired character recall, grapheme deformity and micrographia (progressive reduction in character size during writing) after a lesion that involved the ventral lateral and ventroposterolateral nuclei. Single photon emission computed tomography with a (99m)Tc-ethylcysteinate dimer revealed hypoperfusion in the left precentral gyrus (Brodmann Area 6) and anterior supramarginal gyrus in both. Six months later, the extent of blood flow reduction decreased in the supramarginal gyrus in both patients and the precentral gyrus in patient 1. By this time, the writing impairment improved to nearly the normal range. Our study suggests that kanji agraphia (corresponding to lexical agraphia in Western countries) with poor grapheme formation and micrographia arises from a lesion in the ventral lateral and ventroposterolateral nuclei in the left thalamus. The accompaniment of poor grapheme formation and micrographia may reflect disruption of the cortico-subcortical motor circuit involving the putamen, thalamus, premotor cortex and sensorimotor cortex. It is also suggested that multiple cortical sites can be a target for secondary dysfunction that yields agraphia in a thalamic lesion, and that the recovery of reduced cortical blood flow does not always proceed in parallel with that of agraphia.

Poly(6-(acryloyloxymethyl)uracil) (PAU) having uracil moieties as side chains was synthesized by ordinary radical polymerization to investigate its molecular discrimination for soluble nucleic acid bases in terms of phase transition changes of the polymer aqueous solution. PAU itself in distilled water formed a precipitate due to the polymer complexes at lower temperatures and changed drastically to become water-soluble above a characteristic transition temperature, showing an upper critical solution temperature (UCST). The phase transition behavior was shifted to lower temperatures with increasing concentrations of adenosine (Ado), which is the complementary nucleic acid base to uracil moiety. Ado might interact specifically with uracil moieties of the polymers, preventing the formation of the polymer complex at lower temperatures. Such changes were not observed in PAU aqueous solution containing guanosine (Guo). Additions of Ado and Guo exerted different effects to phase transition changes of the polymer. Moreover, addition of poly(adenylic acid) (Poly(A)) lowered remarkably the transition behavior of PAU solution as compared with Ado addition. It was conceivable that PAU and Poly(A) formed stable polymer complexes, assuming soluble states in even cold water. PAU changed its phase-transition temperature in response to species of the additive materials, demonstrating the specific molecular discrimination in aqueous milieu.

Purpose. To determine aortic endothelial cells permeation ability and mechanisms of the aqueous block copolymeric micelles, poly(ethylene oxide)-poly ((β-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with fluroescein isothiocyanate (FITC) by transport study and confocal laser scanning microscopy.

Purpose. To directly visualize and evaluate the aqueous block copolymeric micelles, poly(ethylene oxide)-poly(β-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with pyrene fluorescence molecule, by nanotechnology of atomic force microscopy (AFM).

Purpose. To design glucose-responsive gels based on the complexation between polymers having phenylboronic acid groups and poly (vinyl alcohol). Specifically, high-glucose sensitivity at physiological pH was achieved through the interaction of phenylborate with amino groups.

Glucose-Sensitive Lower Critical Solution Temperature Changes of Copolymers Composed of N -Isopropylacrylamide and Phenylboronic Acid Moieties

The entrapment of Adriamycin (ADR) in micelles composed of AB block copolymers (poly(ethylene oxide-co-β-benzyl L-aspartate) (PEO-PBLA)) was investigated. The loading process involved transfer of ADR and PEO-PBLA into an aqueous milieu from dimethyl-formamide (DMF) through a dialysis procedure. Evidence for the physical entrapment of ADR in the polymeric micelles was derived from fluorescence spectroscopy and gel permeation chromatography (GPC). The total fluorescence intensity of ADR was low, suggesting that the drug was self-associated in the micelles. In addition, quenching experiments, using a water-soluble quencher (iodide (I–)), showed that the fluorescence of ADR present in micellar solutions was largely unaffected by I–, whereas the fluorescence of free ADR was readily quenched. From Stern-Volmer plots, quenching constants (KSV) of 2.2 and 17 M−l were determined for ADR in micellar solutions and free ADR, respectively. As a result of the entrapment of ADR in the micelles, ADR binds only slightly serum albumin as evidenced by GPC. In contrast, ADR readily binds serum albumin in aqueous solutions. The findings suggest that ADR is stably entrapped in PEO-PBLA micelles. ADR entrapment in polymeric micelles is expected to affect markedly the pharmacokinetics of ADR.

Well-defined poly(ethylene oxide)s with a primary amino group at one end and a hydroxyl group at the other terminus were synthesized with new sila-protected amino functionality initiator, potassium N-[2-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-ethyl]methyl amide [1b]. 1b initiated an anionic polymerization of ethylene oxide (EO) to form a polymer (PEO) without any side reactions such as a cleavage reaction of protective group and a chain transfer reaction. The molecular weights of the PEO determined from GPC and MALDI TOF-MS spectrometry agreed well with those from end group analysis using 1H and 13C NMR and TLC and also with the expected value from EO/initiator ratio. From these results, it was concluded that the polymers thus obtained had a primary amino group at one end and a hydroxy group at the other end and can be regarded as hetrobifunctional PEO.

The micelle-forming behavior of a drug–block copolymer conjugate adriamycm-conjugated poly(ethylene glycol)–poly(aspartic acid) block copolymer; PEG-P[Asp(ADR)] was analyzed by gel permeation chromatography (GPC). Four compositions of the conjugates were observed to form micellar structures in aqueous media, and their micelle-forming behavior was found to be dependent on the composition and media. These micelles did not reach equilibrium within short time periods like low molecular weight surfactants. One composition formed stable micelles in the presence of serum.

Interpenetrating polymer networks (IPNs) composed of poly(acrylamide(AAm)-co-butyl methacrylate (BMA)) and poly(acrylic acid) (PAAc) demonstrate positive swelling changes with an abrupt transition as temperature increases. Temperature-modulated controlled drug release using swelling-shrinking responses of the hydrogels as on-off switches for drug release is reported. The IPNs demonstrate “on” release at higher temperatures. When changing from higher to lower temperatures, an immediate pulsatile drug release is observed followed by a nearly complete “off” state of drug release. The drastic increase of drug release rate is due to mechanical squeezing by a shrinking gel surface layer of the IPNs in response to decreasing temperature. The following decrease of drug release is due to a subsequent formation of a dense layer of polymer at the IPN surface.

A New Model for Zero-Order Drug Release I. Hydrophobic Drug Release from Hydrophilic Polymeric Matrices

MANY polymeric hydrogels undergo abrupt changes in volume in response to external stimuli such as changes in solvent composition1, pH2, electric field3 and temperature4–6. For several of the potential applications of these materials, such as 'smart' actuators, a fast response is needed. The kinetics of swelling and de-swelling in these gels are typically governed by diffusion-limited transport of the polymeric components of the network in water, the rate of which is inversely proportional to the square of the smallest dimension of the gel7–9. Several strategies have been explored for increasing the response dynamics10–14, such as introducing porosity14. Here we show that we can induce rapid de-swelling of a polymer hydrogel by tailoring the gel architecture at the molecular level. We prepare a crosslinked hydrogel in which the polymer chains bear grafted side chains; the latter create hydrophobic regions, aiding the expulsion of water from the network during collapse. Whereas similar gels lacking the grafted side chains can take more than a month to undergo full de-swelling, our materials collapse in about 20 minutes.

Bovine serum albumin and γ-globulin were adsorbed, respectively, on films of ABA-type block copolymers and blendmers composed of 2-hydroxyethyl methacrylate (HEMA) and styrene in a mixture of protein and 0.2 M of phosphate buffer solution (pH 7.4) under the condition of 1/50 physiological concentration of the protein at 37°C. The morphologies and dimensions of the microphase separated structure of the block copolymers and blendmers containing hydrophilic domains of HEMA molecules and hydrophobic domains of styrene molecules were studied by electron microscopy with or without osmium tetroxide fixation. In the adsorption of plasma protein, either both the adsorbed plasma protein and the hydrophilic domains or only the adsorbed plasma proteins could be stained selectively with osmium tetroxide to control the fixation time. Therefore the areas of plasma protein adsorbed on the phase of microseparated structure were evaluated by comparing the micrographs with and without the adsorbed plasma proteins. These results show that bovine serum albumin is adsorbed on the hydrophilic domains escaping from the hydrophobic domains, and on the contrary that γ-globulin is selectively adsorbed on the hydrophobic domains.

The relationship between microphase-separated structures and antithrombogenicities of poly(propylene oxide) (PPO)–segmented polyamides of various polyamide segment lengths was studied. Transmission electron microscopic observation revealed fibrillar lamella structures to be present on the copolymer surfaces. Dynamic mechanical and thermal scanning measurements showed the existence of two mechanical relaxations attributable to micro-Brownian motions of the PPO and polyamide segments, indicating that the PPO and polyamide segments formed distinctly separated microdomain structures. Moreover, wide-angle X-ray diffraction and small-angle X-ray scattering measurements indicated these copolymers to be different in their microstructures with respect to size and distribution of crystalline and amorphous domains even though the crystalline structure was essentially the same as that of nylon 610. The degree of platelet adhesion and aggregation was significantly minimized on the surface of the copolymer, in which the average diameter of the crystalline and amorphous domains were 6.42 nm and 5.18 nm, respectively. This suggests that the size of segmented polyamide microdomains may be a determining factor in antithrombogenicity.

In order to elucidate the interaction between blood platelets and polymer surfaces of microdomain structure, block copolymers consisting of hydrophilic chains of 2-hydroxyethyl methacrylate (HEMA) and hydrophobic chains of dimethylsiloxane (DMS) were synthesized. Films of the HEMA–DMS block copolymers exhibiting hydrophilic–hydrophobic microphase-separated structures were found to enhance platelet adhesion more than homogeneous surfaces of poly(HEMA) or poly(DMS). Platelet adhesion to the block copolymer increased with morphological changes in microdomains so long as the HEMA composition of the block copolymer was 0.90 to 0.58. Platelet adhesion also varied with morphological change in the microdomains caused by changing the casting solvents, though an identical copolymer was employed. These results indicated that platelet adhesion to the HEMA–DMS block copolymer was influenced by domain morphology rather than HEMA composition of the copolymers. In spite of the enhancement of platelet adhesion, the HEMA–DMS block copolymers effectively suppressed shape change and aggregation of adhered platelets. The HEMA–DMS block copolymers were considered to have good antithrombogenecity on the basis of inhibition of activation and aggregation of adhered platelets.