Search

A 58-year-old man presented with an intramedullary spinal cord abscess (ISCA) manifesting as posterior neck pain, gait disturbance, and urinary retention, and transverse myelopathy 1 week later. Magnetic resonance imaging showed the ISCA at the C7 to T1 levels. He was treated under a diagnosis of cryptogenic ISCA with high-dose ampicillin and third- or fourth-generation cephalosporins, which resulted in complete recovery after 2 months. Review of the literature between January 1998 and August 2007 identified 26 cases of ISCA, including our patient. We also identified two additional nonsurgically treated ISCA patients reported between 1977 and 2007. The most common presentation was motor deficits in all patients, followed by fever, pain, and bladder dysfunction. The mortality rate was 1 of 26 patients, and neurological sequelae were observed in 15 of the 25 surviving patients. There was no significant difference in the frequency of neurological sequelae between surgically and nonsurgically treated patients. Mean length of the abscess in the surgically treated group was significantly larger than that in the medically treated group (5.8 vs. 2.2 vertebral bodies). All three nonsurgically treated patients with neurological sequelae had anaerobic infections and received antibiotic therapy later and for shorter periods than those with complete neurological recovery. Antibiotic treatment is comparable to surgery plus antibiotic treatment. Early broad-spectrum high-dose ampicillin and third-generation cephalosporin, covering Gram-positive, Gram-negative, and anaerobic organisms, should be the first choice of management for patients with ISCA.

A patient with progressive anomia and alexia with agraphia for kanji (Japanese morphograms) is described. The patient showed a deficit in single-word comprehension and on-reading (a type of reading that conveys phonetic value) dominance in kanji reading, i.e. on-preceding (pronouncing first with on-reading, irrespective of its preferred reading) and kun-deletion (inability to recall and recognize kun-reading [another type of reading that conveys meaning]) when reading a single-character kanji. These features were due to loss of lexico-semantic information and thus the patient was regarded as having progressive Gogi (word-meaning) aphasia by Imura, a Japanese manifestation of semantic dementia. Macroscopically, neuropathological examination disclosed atrophy of the left frontotemporal lobe with accentuation in the anterior portion of the temporal lobe. Histologically, there was neuronal loss in the cerebral cortex, hippocampus, parahippocampal gyrus, amygdala, caudate nucleus, and putamen. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells. This case demonstrates that progressive Gogi aphasia is semiologically identical to semantic dementia, and our patient clinicopathologically resembled those of Rossor et al. [Rossor, M.N., Revesz, T., Lantos, P.L., Warrington, E.K. Semantic dementia with ubiquitin-positive tau-negative inclusion bodies. Brain 2000; 123: 267-76.] and Hodges et al. [Hodges, J.R., Davies, R.R., Xuereb, J.H., Casey, B., Broe, M., Bak, T.H., et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004; 56: 399-406.].

The hydrophobic monomer, n-butyl methacrylate (BMA) has been incorporated into thermoresponsive poly(N-isopropylacrylamide) (PIPAAm) to lower PIPAAm phase transition temperatures necessary for systematically regulating cell adhesion on and detachment from culture dishes at controlled temperatures. Poly(IPAAm-co-BMA)-grafted dishes were prepared by electron beam irradiation methods, systematically changing BMA content in the feed. Copolymer-grafted surfaces decreased grafted polymer transition temperatures with increasing BMA content as shown by water wettabilities compared to homopolymer PIPAAm-grafted surfaces. Bovine endothelial cells readily adhered and proliferated on copolymer-grafted surfaces above collapse temperature at 37°C, finally reaching confluence. Cell sheet detachment behavior from copolymer-grafted surfaces depended on the culture temperature and BMA content. In conclusion, cell attachment/detachment can be controlled to an arbitrary temperature by varying the content of hydrophobic monomer incorporated into PIPAAm grafted to culture surfaces. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 70–78, 2004

Vitamin B12 deficiency mainly affects the dorsal column. In this study, we investigated which part of the sensory pathway is affected in vitamin B12 deficiency using NCS and SEPs. We retrospectively reviewed EMG database of Teikyo University and Mitsui Memorial Hospital from 2008 to 2016, and enrolled patients who presented with sensory symptoms and/or gait disturbance, and whose serum B12 level was below 170 ng/ml. Enrolled were 17 patients. Spinal MRI demonstrated abnormalities in 4/17. NCS was abnormal in 3/15 patients for the sural nerve and in 5/12 patients for the median nerve. When NCS and peripheral segments of the SEPs were combined, conduction delay was detected in 12/15 patients for the lower limb and 8/13 patients for the upper limb. Delay of the central conduction was rarer, 3/15 patients in tibial SEPs. N9o to P13/14o segment in median SEPs was abnormal in 4/8 patients, although this is a mixture of the peripheral and central conductions. Vitamin B12 deficiency patients showed abnormalities of the peripheral nerve conduction more frequently than those of the central conduction. SEPs are useful in localizing the lesion along the sensory pathway, not only for CCT but for peripheral conduction.

We herein report the case of a 65-year-old woman who presented with the subacute onset of dementia and subsequently developed abnormal behavior and a gait disturbance. Her condition transiently improved; however, within one month, she became drowsy and poorly responsive, with limb chorea and urinary incontinence. Her history of frequently using charcoal led us to diagnose her with carbon monoxide (CO) poisoning. The findings of this case and a literature review suggest that subacute dementia due to CO poisoning recovers late, after a year or more, in patients above sixty years of age, and both hyperbaric oxygen and corticosteroid pulse therapy should be considered in such cases, even after one month.

We show the result of pre-clinical study of NK911, a polymeric micelle carrier system for doxorubicin (DOX). The NK911 micelle carrier consists of polyethyleneglycol and conjugated doxorubicin-polyaspartic acid. It has high hydrophobic inner core, and therefore can entrap the sufficient amount of DOX. NK911 has a small particle size of about 40 nm in diameter that accumulates in tumor tissue by EPR effect showing much stronger activity than the free DOX. We plan to perform a clinical trial at National Cancer Center Hospital, Japan from 2001.

The authors report a patient with pure alexia (letter-by-letter reading) selectively impaired for kana (Japanese phonograms), cerebral achromatopsia, and right lower quadrantanopsia after hemorrhage in the left posterior occipital lobe, mainly under the lateral occipital gyri. The patient also could not recognize some single-character kana, nor could he discriminate between two shapes of a similar size. The authors believe that the posterior occipital lobe, including the lateral occipital gyri, is specialized to recognize kana characters in this patient.

漢字単語, 仮名単語, 無意味仮名文字列を5人ずつ別々の被験者群に音読させ, その賦活領域をStatistical Parametric Mapping (SPM) で解析した.漢字単語, 仮名単語で共通に賦活されたのは, 上側頭回後部, 舌状回, 下後頭回, 紡錘状回・下側頭回であり, 漢字では紡錘状回・下側頭回が, 仮名では下後頭回が目立って賦活された.これらは漢字と仮名の読みの過程に異なる部分があることを示唆する.さらに仮名単語を別の被験者5人に黙読させた時の局所脳血流の変化をSPMで解析した.黙読から凝視点固視課題を引いたのみでは前方領域で賦活されたところはなかった.音読から黙読を画像上引くと, 一次感覚・運動野, Broca野の一部 (44野) , 補足運動野, 島回前部が賦活されたが, これらは構音・発声に関わると考えられ, 他方音読と黙読に共通して中心前回前部, 頭頂弁蓋内側, 上側頭回中部が賦活されたが, これらは読みそのものに関わると考えられた.

We evaluated the alexia and agraphia of three patients with different lesions using Japanese kanji (morphograms) and kana (phonograms) and made a lesion-to-symptom analysis. Patient 1 (pure alexia for both kanji and kana and minor agraphia for kanji after a fusiform lesion) made more paragraphic errors for kanji, whereas patient 2 (alexia with agraphia for kanji after a posterior inferior temporal lesion) showed severe reading and writing disturbances and more agraphic errors for kanji. Brodmann Area 37 was affected in both patients, but in patient 2 the lesion was located lateral to that in patient 1. Patient 3 showed agraphia without alexia after restricted lesion to the angular gyrus. We believe that pure alexia (patient 1) results from a disconnection between the medial fusiform gyrus and posterior inferior temporal area (the lateral fusiform and inferior temporal gyri), whereas alexia with agraphia for kanji (patient 2), corresponding to lexical agraphia in Western countries, results from damage to the posterior inferior temporal area, in which whole-word images of words are thought to be stored. Furthermore, restricted lesion in the angular gyrus (patient 3) does not produce alexia; the alexic symptom of “angular” alexia with agraphia may be the result of damage to the adjacent lateral occipital gyri.

Fabrication of functional tissue constructs using sandwiched layers of cultured cells could prove to be an attractive approach to tissue engineering. Rapid detachment of cultured cell sheets is a very important recovery method that permits facile manipulation of the sheet and prevents functional damage. To accelerate the required culture substrate hydrophilic and hydrophobic structural changes in response to culture temperature alteration, poly(N-isopropylacrylamide) (PIPAAm) was grafted onto porous culture membranes by electron beam irradiation. Analyses by attenuated total reflection-Fourier transform IR and electron spectroscopy for chemical analysis revealed that PIPAAm was successfully grafted to surfaces of porous membranes. Atomic force microscopy (AFM) results showed that PIPAAm-grafted membranes had smoother surfaces than ungrafted controls while retaining their porous structure. The mean roughness of PIPAAm-grafted and -ungrafted porous membrane surfaces determined by digital AFM autocalculation was 4.40 +/- 0.4 and 5.9 +/- 0.4 nm, respectively. Tissue culture polystyrene (TCPS) dishes grafted with PIPAAm were compared with PIPAAm-grafted porous membranes in cell sheet detachment experiments. Approximately 75 min was required to completely detach cell sheets from PIPAAm-grafted TCPS surfaces compared to only 30 min to detach cell sheets from PIPAAm-grafted porous membranes. With porous membranes, the water accesses the PIPAAm-grafted surface from underneath and peripheral to the attached cell sheet, resulting in rapid hydration of grafted PIPAAm molecules and detachment of the cell sheet. With TCPS PIPAAm-grafted surfaces the water is supplied from only the periphery of a cell sheet, slowing detachment.

Lectin-like function was demonstrated in this study for a novel water-soluble polymer with phenylboronic acid residues (poly (AAPBA-DMAm)), which induced appreciable proliferation of murine spleen lymphocytes with an increased expression of interleukin-2 (IL-2) receptor on their surface. Consequently, boosted proliferation of lymphocytes with cytotoxic action to YAC-1 cells was achieved by concurrent addition of IL-2 with poly(AAPBA-DMAm) in the medium, indicating this boronate-containing polymer to be worked as an effective immuno-adjuvant for the induction of lymphokine-activated killer (LAK) cells. Flow-cytofluorimetry study revealed that poly(AAPBA-DMAm) competitively inhibited the cellular binding of N-acetylneuraminic acid-specific lectin (Limax Flavus Agglutinin) in a concentration-dependent manner, suggesting that phenylboronate moiety in the polymer may recognize N-acetylneur- aminic acid (sialic acid) residues existing on the plasma-membrane surface of lymphocytes to induce their proliferation.

To investigate the influence of molecular architecture of poly(acrylic acid) (PAAc)-graft-poly(N,N-dimethylacrylamide) (PDMAAm) (PAAc-g-PDMAAm) on its solution properties in aqueous media, graft copolymers were synthesized by free radical copolymerization of AAc with PDMAAm macromonomer. PAAc-g-PDMAAms were water-soluble at lower temperatures, while they showed a liquid−liquid phase separation from water above the characteristic transition temperatures. The phase transition behavior was affected by the copolymer compositions and pH of the solution. Below the transition temperature, hydrogen-bonding formation between AAc and DMAAm units was observed in the PAAc-g-PDMAAm aqueous solution by FT-IR−ATR measurement. Graft copolymers were thus formed spherical associates with a diameter of ca. 150 nm estimated from the dynamic light scattering measurement. At higher temperatures, the dehydrated regions and the weak dehydration of the PDMAAm chains induced cooperatively the hydrophobic aggregation, resulting in ...

Adriamycin (ADR) dimer was prepared and its antitumor activity was evaluated with mouse colon adenocarcinoma 26 (C 26). As compared with original ADR, the dimer did not show significant antitumor activity, either in vitro or in vivo. Furthermore, polymeric micelles containing varied ratios of the dimer to the original ADR were prepared. Polymeric micelles with a higher dimer/ADR ratio (9.7) showed significant antitumor activity, but the effective dose shifted higher. Effective doses were found to largely depend on the concentration of the original ADR, rather than that of the dimer at the tumor sites. Therefore, it was presumed that the original ADR played a major role in antitumor activity, and the dimer played a supplementary role to contribute selective delivery of ADR to the tumor sites.

To fabricate peptide delivery systems using polymeric drug carriers, an oligopeptide model drug, [Arg8]-vasopressin(AVP), was incorporated into nano-associates comprising poly(ethylene glycol)-( l -aspartic acid block copolymer (PEG-P(Asp)). Incorporation of the AVP was accomplished using a dialysis method. Static light scattering measurements revealed that the acid-type and mixture-type PEG-P(Asp)s formed nano-associates independently without AVP, while the salt form PEG-P(Asp) did not. High loading of AVP into acid-type PEG-P(Asp) was observed with loading levels controlled by changing the molar ratio of drug and block copolymer. Mixture-type PEG-P(Asp) did not show high loading and the salt-type PEG-P(Asp) form did not at all. Acid-type P(Asp) homopolymer formed associates including AVP, however, it was insoluble in aqueous medium. Dynamic light scattering measurements showed that the acid-type PEG-P(Asp) associates sizes narrowly clustered around 150 nm. This finding suggests that associates of acid-type PEG-P(Asp) effectively incorporates peptides possibly via a hydrogen bonding interaction between the block copolymer and the peptide.

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.

To achieve a combination of spatial specificity in a passive manner with a stimuli-responsive targeting mechanism, a temperature-responsive polymeric micelle is prepared using block copolymers of (poly(N-isopropylacrylamide-b-butylmethacrylate) (PIPAAm-PBMA)). The micelle inner core formed by self-aggregates of PBMA segments successfully loaded with a drug (adriamycin), and the outer shell of PIPAAm chains played a role of stabilization and initiation of micellar thermo-response. Optimum conditions were investigated for the micelle formation and drug loading into the inner cores in a view of micellar stability and function as drug carriers. Outer shell hydrophilicity that prevents inner core interaction with biocomponents and other micelles can be suddenly switched to hydrophobic at a specific site by local temperature increase beyond the LCST (lower critical solution temperature) (32.5 degrees C). These micelles showed reversible structural changes allowing drug release upon heating/cooling thermal fluctuations through the LCST. Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure. The reversible and sensitive thermo-response of the micelle opens up opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.

WWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWWW Poly(ethylene glycol-b-lactide) possessing a methoxygroup at the poly(ethylene glycol) (PEG) chain end anda polymerizable methacryloyl group at the poly(lacticacid) (PLA) chain end (MeO–PEG/PLA–methacryloyl)was prepared by an anionic ring-opening polymerizationof ethylene oxide and DL -lactide in tandem mannerinitiatedwithapotassium2-methoxyethanolate,followedby end-capping with an excess of methacrylic anhydride.The molecular weight of the obtained polymer wascontrolled by the initial monomer/initiator ratio, whichwas confirmed by the combination of gel permeationchromatography and nuclear magnetic resonance ana-lyses. The functionality of the methacryloyl–PLA endwas almost quantitative. The MeO–PEG/PLA–metha-cryloyl (38/35; these numbers in parentheses denote themolecular weights of PEG and PLA segments divided by100, respectively) formed a core–shell type sphericalmicelle in aqueous media obtained by a dialysistechnique, the cumulant diameter of which was ca.30nm with very low polydispersity factor.The methacryloyl group adjacent to the PLA waspolymerized in the PLA core of the micelle. Thepolymerizationproceededthermallywithradicalinitiatorand photochemically with photo-initiator to producecore-polymerized nanoparticles, which was found byspectroscopic and light-scattering techniques. Taxol-incorporated micelles were prepared to entrap Taxol intoMeO–PEG/PLA–methyacryloyl block copolymer mi-celles by the oil/water emulsion method. Copyright O1999 John Wiley & Sons, Ltd.KEYWORDS: polymeric micelle; stable nanoparticle;drugdeliverysystem;PEG/PLAblockcopolymer;micellestability; taxol

Adriamycin (ADR)-loaded thermally responsive polymeric micelles composed of poly( N -isopropylacrylamide- co - N , N -dimethylacrylamide)- b -poly( d,l -lactide) were prepared by dialysis from its dimethylacetamide solution against water. Microfiltration was successfully applied to removal of block copolymer associates, which were smaller than micellar structures. By this microfiltration polymeric micelles showing a lower critical solution temperature (LCST) at 40°C in phosphate buffered saline was obtained with a monodispersed size distribution of 69.2 nm in cumulant average diameter. ADR-loaded micelles released more ADR at 42.5°C (above the LCST) than at 37°C (below the LCST). ADR-loaded micelles did not show much cytotoxic activity against bovine aorta endothelial cells at 37°C, in contrast to high cytotoxicity at 42.5°C. On the other hand, free ADR expressed high cytotoxicity at both the incubation temperatures. Thus, thermally responsive polymeric micelles showed distinct control of ADR cytotoxic activity by temperature, while free ADR did not. From these results, an effective target therapy against solid tumors is feasible for these polymeric micelles by a combination of selective delivery to tumor sites based on stable micellar structures at 37°C and enhanced cytotoxic activity of these drug-loaded micelles at 42.5°C by local heating at tumor sites.

Four types of hydrophilic gel microcapsules containing water have been prepared by an interfacial polymerization method. Each type of microcapsules has a membrane of different composition. Using three kinds of monomers, N,N-dimethylacrylamide (DMAAm), 4-(aminomethyl)styrene (AmSt), and N,N-dimethylaminopropylacrylamide (DMAPAA), one type of aqueous copolymer having primary and tertiary amino groups was obtained. By the polymerization of three kinds of monomers, DMAAm, AmSt, and 2-[(methacryloyloxy)ethyl] trimethylammoniumchloride (METAC), another type of aqueous copolymer having primary and quaternary ammonium groups was also obtained. Two more types of copolymers were synthesized by copolymerization of α-acryloxy-ω-methoxy-poly(ethylene glycol) (a-PEG) with the above two kinds of monomer mixture. These copolymers were polymerized with terephthaloyldichloride at the water/oil interface to prepare four types of microcapsules containing water, i.e., poly(DMAAm-co-DMAPAA-co-AmSt-alt-terephthalic acid) microcapsules, poly(DMAAm-co-DMAPAA-co-AmSt-co-PEG-alt-terephthalic acid) microcapsules, poly (DMAAm-co-METAC-co-AmSt-alt-terephthalic acid) microcapsules, and poly (DMAAm-co-METAC-co-AmSt-co-PEG-alt-terephthalic acid) microcapsules, which will be abbreviated to MC 1, MC 2, MC 3, and MC 4, respectively. It has been predicted that the microcapsule membranes are hydrophilic and soft and have two-sublayer structures from electrophoretic mobility measurements and from the analysis of the data with Ohshima’s electrokinetic theory for soft particles. The outer sublayers of MC 1 and MC 2 are negatively charged and those of MC 3 and 4 are slightly positively charged. Also, the surfaces of MC 1 and MC 2 are harder than those of MC 3 and 4. By PEGylation, the surface charge density in the membranes decreases and the surface becomes softer. It has been found that the membrane of red blood cells (RBC) is also soft and is composed of two-sublayers, the outer sublayer of which is negatively charged and the inner one is positively charged. The interaction of four types of microcapsules with RBC has been studied. It was found that microcapsules with soft surfaces (MC 3 and MC 4) do not interact with RBC, even though the microcapsule surfaces are positively charged and the surface of RBC is negatively charged. On the other hand, microcapsules with negatively charged but harder surfaces (MC 1) interact with RBC to introduce hemolysis. The membrane surface of MC 2, which is obtained by PEGylation of MC 1, becomes softer than that of MC 1 so that the interaction with RBC was weakly suppressed. From these, it was concluded that the dominant factor to control the interaction between synthetic polymer surfaces and biological cell surfaces is not the surface charges carried by the polymer surfaces but the softness of the polymer surfaces.

Thermally-responsive culture surfaces were designed using copolymers of N-isopropylacrylamide, 4-(aminomethyl)styrene, and acrylic acid. These surfaces contained functional amine and carboxyl groups, which allowed biomolecules to be grafted by amide formation. Epidermal growth factor (EGF), and extracellular matrix (ECM) molecules (collagen type IV, and chondroitin sulfate) were investigated, as surface-grafted biomolecules, for their ability to stimulate cell attachment, proliferation, and function by signaling only from the basal side of cultured cells. Surface analysis of biomolecule-grafted porous inserts showed covalent binding of biomolecules to either amine or carboxyl groups. Multiple attachment to amine and/or carboxyl groups served as cross-linking points that made the polymer hydrogel permanently adherent to the culture surface. Immunofluorescence microscopy techniques gave positive identification of grafted biomolecules. Grafting of EGF improved cell proliferation versus that on nongrafted controls, or controls grafted only with ECM molecules. ECM grafting induced cell attachment on attachment-resistant surfaces. Analysis of trans-epithelial resistance, fluid transport, and polarized g-glutamyl transpeptidase activity indicated that simultaneous grafting of both EGF and ECM produced better polarized cell function than nongrafted controls, or controls grafted with only one type of biomolecule. Covalent grafting of biomolecules did not interfere with cells ability to detach from thermally responsive surfaces upon temperature decrease.

Interaction between protein and cell was discussed using bovine serum albumin (BSA) and yeast protoplast. Glutaraldehyde was used for crosslinking intracellular and intrinsic membrane proteins, which enabled experiments to be carried under various conditions such as pH, salt, and temperature. BSA bound to the surface of yeast protoplast mainly due to the electrostatic interaction, which was determined by investigating the surface potential of the protoplast and the binding isotherms at various pHs. The BSA binding demonstrated the modified Langmuir type and the binding constants and cooperativity parameters were calculated. At the isoelectric point of both BSA and protoplast, the amount of binding obtained the maximum, while at lower and higher pH the binding was significantly decreased. The binding was further discussed in terms of lipid fluidity of the protoplast.

Cross-linked poly(N-isopropylacrylamide) (PIPAAm) hydrogel-modified surfaces were prepared to investigate the effects of a three-dimensionally cross-linked structure of PIPAAm layers on both wettability changes and hydrophobic interactions with hydrophobic solutes in response to temperature changes. The temperature-responsive surface was prepared by polymerization of IPAAm in the presence of cross-linker on the substrates on which an azo polymerization initiator was covalently bonded. The PIPAAm hydrogel-modified surface showed temperature-responsive hydrophilic/hydrophobic surface property alterations as demonstrated by a large and discontinuous wettability changes in a range of 27−32 °C, a slightly lower temperature range than the phase transition temperature for soluble PIPAAm in aqueous media. This implies that the dynamic motion in response to temperature for PIPAAm segments in the modified hydrogel is restricted due to the cross-linked structure. The effect of the three-dimensional PIPAAm structure ...

We have developed a new cell culture substrate grafted with a temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm) using an electron beam irradiation method. These surfaces are hydrophobic in culture at 37 degrees C due to the hydration/dehydration changes intrinsic to PIPAAm at 32 degrees C, and they become highly hydrophilic below 32 degrees C. At 37 degrees C grafted and ungrafted surfaces showed no difference with regard to attachment, spreading, growth, confluent cell density, and morphology of bovine aortic endothelial cells. Stress fibers, peripheral bands, and focal contacts were established in similar ways. After the medium temperature was decreased to 20 degrees C, spread cells lost their flattened morphology, acquiring a rounded cell appearance similar to that of cells immediately after plating. After mild agitation cells floated free from the dish surface without trypsin treatment. Neither cell morphological changes nor cell detachment occurred on ungrafted surfaces. An ATP synthesis inhibitor, sodium azide, and a tyrosine kinase inhibitor, genistein, suppressed cell morphological changes and cell detachment while a protein synthesis inhibitor, cycloheximide, slightly enhanced cell detachment. An actin filament stabilizer, phalloidin, and its depolymerizer, cytochalasin D, also inhibited cell detachment. These findings suggest that cell detachment on grafted surfaces is mediated by intracellular signal transduction and reorganization of the cytoskeleton. While trypsinization causes damage to the cell membrane surface and extracellular matrix proteins, this alternative low temperature treatment is exceptionally noninvasive. The temperature-responsive cell culture surface also should prove useful for investigating the molecular machinery involved in cell-surface detachment.

Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.

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.

For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we have successfully incorporated KRN5500 into polymeric micelles. In the present study, in vitro and in vivo anti-tumor activity against several human tumor cell lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m) were evaluated in comparison with those of the prototype KRN5500. KRN/m was found to express similar antitumor activity to KRN5500 in the in vitro and in vivo systems. However, the vascular damage and liver focal necrosis observed with KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore, we expect that KRN/m will be superior to KRN5500 for clinical use and that the methodology of polymeric micelle drug carrier systems can be applied to other water-insoluble drugs.

Block copolymer micelles (polymer−metal complex micelles) containing platinum(II) complexes in the core were prepared through the complexation of cis-dichlorodiammineplatinum(II) (cisplatin, CDDP) with poly(ethylene glycol)−poly(α,β-aspartic acid) block copolymer (PEG−P(Asp)) in an aqueous medium. Dynamic light scattering measurements revealed that CDDP-complexed micelles had diameters of approximately 20 nm with considerably narrow distribution. The critical substitution molar ratio of CDDP to Asp residues in PEG−P(Asp) (CDDP/Asp) to form a stable micelle structure was determined to be 0.5. The CDDP-complexed micelle, which was stable in distilled water at room temperature, started to dissociate in approximately 10 h of the induction period accompanying the sustained release of platinum(II) complex from the micelle in physiological saline (0.15 M NaCl solution) at 37 °C. The release rate of CDDP was inversely correlated with the chain length of P(Asp) segments in the block copolymer. This property of sus...

Four types of hydrophilic gel microcapsules containing water have been prepared by an interfacial polymerization method. Each type of microcapsules has membranes of different compositions. By the combination of three kinds of monomers, N , N -dimethylacrylamide (DMAAm), 4-(aminomethyl)styrene (AmSt), and N , N -dimethylamino-propylacrylamide (DMAPAA), two types of water-soluble copolymers having tertiary amino groups were obtained. Two more types of copolymers were synthesized by copolymerization of above three monomers with α -acryloxy- ω -methoxy-poly(ethylene glycol) (a-PEG). These four types of copolymers were polymerized with terephthaloy-dichloride at the water/oil interface to prepare four types of microcapsules containing water. Effects of the stirring rate during the preparation of microcapsules upon the membrane properties were studied. The effects of relative permittivity of dispersing media on microcapsule sizes were studied. It was found that the microcapsule sizes are controlled by the composition of the membranes and by the relative permittivity of the solvents in which microcapsules are redispersed. Depending on the stirring rates during the preparation procedure, the different changes in microcapsule size were observed during the exchanges of dispersing media of various relative permittivities. From these results, it is concluded that different microcapsules in their membrane compositions and in their properties are obtained depending on the stirring rate during the preparation of microcapsules, even if other preparation conditions are kept constant.

Deswelling mechanism for comb-type grafted poly( N -isopropylacrylamide) (PIPAAm) hydrogel was investigated to make clear the effect of gel architecture on the gel deswelling kinetics. Deswelling rate and mechanism were compared with those for conventional crosslinked PIPAAm gel and poly(ethylene oxide) (PEO)-grafted PIPAAm gel in response to temperature increase from below to above the gel-phase transition temperatures. The deswelling rate for the conventional PIPAAm gel are reciprocal to the gel size square, indicative of collective diffusion mediated manner for crosslinked network into water. Although PEO graft chains formed water release channels within the network to produce fast gel deswelling changes, deswelling change of PEO-grafted gel also demonstrated collective diffusion mediated manner of crosslinked backbone chains. On the other hand, one order faster rate of deswelling change of PIPAAm-grafted gel was observed than that of PEO-grafted gel with identical gel dimension. The deswelling change of PIPAAm grafted gel did not obey collective diffusion mediated manner, demonstrating reciprocal to the gel size to 1.58th power. This deswelling mechanism was explained in terms of rapid hydrophobic aggregation of freely mobile PIPAAm graft chains and an operation of intrinsic elastic forces of polymer network. The operation of both elastic force and strong hydrophobic aggregation force between the dehydrated PIPAAm graft chains released water inside the gel, causing more rapid deswelling changes of the PIPAAm-grafted gels.

Poly(ethylene oxide) (PEO) chains are introduced as graft chains maintaining freely mobile ends in thermo-responsive cross-linked poly(N-isopropylacrylamide) (PIPAAm) hydrogels by copolymerization of IPAAm with α-acryloyl-ω-methoxy-PEO. The deswelling response on raising the temperature of this gel above the gel phase transition temperature (TP) takes place within 10 min, whereas a conventionally cross-linked PIPAAm gel of the same dimensions requires 1 month for deswelling. This difference is due to the formation of water release channels within the skin layer by the hydrophilic PEO graft chains. The rapid deswelling of the grafted gel is compared with the deswelling changes of random copolymer gels composed of IPAAm and hydrophilic acrylic acid (AAc), which also accelerates gel deswelling. Deswelling is fastest in copolymers containing 1.3 wt % AAc and in grafted gels containing 13 wt % PEO. These results were interpreted as reflecting the gel structure.

We describe a patient with progressive aphemia with agrammatism that was later overlaid with buccofacial apraxia and pseudobulbar palsy. Pathological findings were consistent with those of classic Pick's disease with argyrophilic inclusions and neuronal achromasia, except for restricted cortical atrophy in the frontal operculum posterior to the pars opercularis (Brodmann Area 44). In addition, major neuronal loss was confined to the premotor cortex and the anterior half of the precentral gyrus (Area 6), which apparently explained the aphemia. The present case demonstrated that classic Pick's disease can show quite limited cortical atrophy in a patient who clinically presents with progressive aphemia. Also, our patient differed from the progressive non-fluent aphasia patients reported as having Pick's disease, who were all Pick variants, revealing that classic Pick's disease can be included in the spectrum of progressive aphasia syndrome.

A novel UV crosslinkable co-polymer of 4-(N-cinnamoylcarbamide)methylstyrene (CCMS) and N-isopropylacrylamide (IPAAm) was partially entrapped in traditional tissue-culture-treated polystyrene and crosslinked by UV light irradiation. Dishes modified by this method showed a change in contact angle with respect to temperature as compared to tissue culture polystyrene controls. Surface chemical analysis indicated that the crosslinked hydrogel does not detach from the surface after successive rinsing in ethanol and water, keeping the cells or cell construct free of unwanted soluble polymer after detachment. Cultures of both bovine endothelium and human retinal pigmented epithelium were confirmed to be able to attach and grow on the polymer-modified surfaces morphologically identical to that on control tissue culture polystyrene surfaces. Corresponding to a change in temperature, these cultures would detach and could be transplanted to another culture surface without functional and structural changes. These results show that the new, photo-crosslinkable hydrogel system can utilize the hydrophobic/hydrophilic change of the surface for cell culture detachment while being permanently applicable to any tissue culture geometry. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 631–639, 1998.

Interaction of rat lymphocyte subpopulations (B cells and T cells) with surfaces of poly ( N,N -dimethylacryl-amide- co -3-acrylamidophenylboronic acid) (DB copolymers) with varying composition was evaluated under a controlled shear stress by using a plane-parallel-type channel equipped with a polymer-coated bottom wail [field-flow fractionation/ adhesion chromatography (FFF/AC)]. This method enables to control the hydrodynamic shear stress at the channel wall resulting from the parabolic flow in the channel. The recovery profile of lymphocytes from DB channels was different among each subpopulation, and the selective recovery of T cells from the channel was achieved with most of B cells remaining in the channel. Phenylboronic acid residues in DB copolymers seem to work as binding sites for sugar residues, presumably sialic acid residues, existing on the membrane surface of lymphocytes. Yield and efficiency of the separation are in the practical range for the application in immunological field, allowing this system to be useful as a novel lymphocyte separator.

To evaluate the role of the sub-cortical white matter and cortical areas of the supramarginal gyrus in short-term memory impairment (shortened digit or letter span) and repetition difficulty, four patients with conduction aphasia and impaired short-term memory and two patients with only short-term memory impairment were given digit span, letter span, speech audiometry and dichotic listening tests. The results showed that in most of the patients letter span was inferior to digit span and that bilateral ear suppression in the dichotic listening test was observed in two patients with a lesion in the inferior part of the supramarginal gyrus, suggesting that what was affected was phonological information and that the supramarginal gyrus was the storage site. The overlapped lesion of conduction aphasia patients with short-term memory impairment was the periventricular white matter at the upper to middle part of the trigone, while patients with only short-term memory impairment had a lesion in the inferior supramarginal gyrus in common. Thus, damage to the periventricular white matter at the trigone may yield the phonemic paraphasia characteristic of conduction aphasia, while damage to the inferior part of the supramarginal gyrus may result in the impairment of short-term memory. We believe that as a part of the mechanisms of short-term memory and repetition, phonological information is processed in the primary auditory cortex and goes through the periventricular white matter to the inferior part of the supramarginal gyrus and is temporarily stored there.

An anticancer drug adriamycin (ADR) was incorporated into polymeric micelles forming from poly(ethylene glycol)-poly(aspartic acid) block copolymer by chemical conjugation and physical entrapment. Structural stability of the polymeric micelles was found to be dependent on both the contents of chemically conjugated and physically entrapped ADR. The polymeric micelle with high contents of the chemically conjugated ADR and the physically entrapped ADR expressed very high in vivo antitumor activity against murine C 26 tumor, while the polymeric micelle with only the chemically conjugated ADR showed negligible in vivo activity. This indicates that the physically entrapped ADR played a major role in antitumor activity in vivo. For the polymeric micelle with the high ADR contents, it was found that a dimer of adriamycin molecules formed and that this dimer was physically entrapped in the inner core of the micelle as well as intact ADR.

本研究では, グラフト鎖を有する分子構築ゲルにより, 温度変化に応答して素早く膨潤・収縮変化するゲルを実現し, 三次元網目鎖の凝集による水の押し出しと同期させて薬物をパルス的に放出する, 薬物放出制御の実現を目的として研究を行った.温度応答性ポリN-イソプロピルアクリルアミドの三次元網目中に, ポリエチレングリコールをグラフトしたゲルを合成した.ゲルは昇温変化で膨潤状態から収縮状態へと変化するとき, グラフ鎖が水のチャンネルを形成することにより, 主鎖の網目の凝集変化にともなうゲル内の水を素早くゲルの外へ押し出す透過チャンネルの役目を果たし, ゲルは素早く収縮変化した.これは, 三次元網目構造のポリN-イソプロピルアクリルアミドゲルが収縮変化するとき, 表面に緻密な高分子鎖からなるスキン層を形成し, 水の透過を抑制するため, ゲルの収縮変化がゆっくりとなるのときわめて対照的であった.さらに, ゲルの収縮変化にともなう薬物放出挙動が, 従来のゲルとグラフト型ゲルで大きく異なることが明らかにされた.すなわち, 従来のゲルが透過性の低いスキン層を形成し薬物拡散を抑制するのに対し, グラフト型ゲルは収縮変化による水の押し出しと同期させて, 内包した薬物を一気に押し出して放出し, パルス型の薬物放出挙動を示した.このグラフト鎖を有する分子構築ゲルによる, 温度応答性の薬物放出制御の特性を薬物の分子量を変化させて検討した.水の押し出し挙動と放出される薬物の分子量との相関を, 従来型のPIPAAmゲルの場合と比較しながら詳細に議論した.

Temperature-responsive hydration/dehydration changes in surface-grafted poly(N-isopropylacrylamide) (PIPAAm) were utilized for hydrophilic/hydrophobic surface property alterations in cell culture. In this report, we utilized PIPAAm-grafted surfaces to recover confluently-cultured vascular endothelial cells as coherent monolayers from this cell culture substrate and to transfer to new cell culture substrates. For this purpose, we used two different methods to recover and transfer cell monolayer cultures: (1) chitin membranes used as an apical side cell support during cultured cell transfer, allowing cell basal side reattachment to new culture substrates after transfer; and (2) a cell culture insert (porous PET) used as both a support as well as new substrate, allowing basal surfaces of cultured cells to be exposed to the medium after transfer. In both cases, all cells grown on PIPAAm-grafted surfaces detach completely with maintenance of basement membrane-like structure. Recovered cells attach to the second culture surfaces, covering more than 60% of the new substrate, and retain approximately 90% viability and their original function as judged from tissue-type plasminogen activator secretion. This technique could be utilized to prepare novel bioartificial organs as well as cell co-culture systems by multi-layering different cell types to mimic tissue structures for tissue engineering.

Novel hydrophilic-hydrophobic block copolymers - poly(2-hydroxyethyl methacrylate-block-4-bis(trimethylsilyl)methylstyrene) (poly(HEMA-block-BSMS) or BH polymer) - were prepared as materials potentially useful for blood-contacting devices. Among the BH(X) series including poly(HEMA) itself, platelet adhesion and activation are minimum on the surface of BH(10), the block copolymer composed of 10 mol% of the hydrophobic segment. The unique physicochemical characteristics of BH(10) such as the high free water content and the increased mobility of PHEMA segments seem to play an important role in the prevention of platelet adhesion and activation. The water content of BH(10) was twice that of poly(HEMA) itself, even in the presence of 10 mol% of the hydrophobic moiety [poly(BSMS)]. Further, an anomalous increase in free water content was observed for the BH(10) sample measured by DSC. The glass transition temperature of BH(10) in the dry state was determined to be c. 10 degrees C, which was much lower than that observed for each of the homopolymers (c.f.: Tg [poly(HEMA)] = 70 degrees C; Tg [poly(BSMS)] = 160 degrees C), suggesting an increased mobility of tethered PHEMA segments in the BH(10) film.

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).

Copolymers (IABb) composed of N-isopropylacrylamide (I), N-(3-dimethylaminopropyl)-acrylamide (A), 3-acrylamidophenylboronic acid (B), and a hydrophobic comonomer, n-butyl methacrylate (b), were synthesized as cell culture substrata since we previously learned that bovine aortic endothelial cells (BAECs) cultured on the phenylboronic acid-containing copolymer (IAB) differentiated into capillary structures after 26 days culture. The synthesized IABb copo ymers contained higher boron and amine moieties than the IAB copolymer. The results of the dynamic contact angle measurement revealed that IABb copolymer-coated surfaces showed a relatively hydrophobic nature, changing to hydrophilic in response to the aqueous environment. BAECs cultured on the copolymer substrata developed into capillary networks after 7 days. This is probably due to the enrichment of boron and amine segments in the vicinity of the hydrophilic copolymer surface, enhancing more pronounced interaction of boronates with cell membrane glycocalyx. The introduction of n-butyl methacrylate into the polymers might enhance the diffusion of the hydrophobic segments to the bulk polymers and the concentration of relatively hydrophilic segments at the outermost polymer surfaces by contact with water. A copolymer (IAP) without boronic acid groups was also prepared using N-phenylacrylamide (P) as a comonomer instead of 3-acrylamidophenylboronic acid in the IAB copolymer to investigate the effect of boronic acid moieties on the capillary formation of the cultured cells. Although the endothelial cells seeded on the copolymer without boronic acid groups adhered during the early culture period, these cells showed neither proliferation nor differentiation and detached from the surface after 13 days. These results strongly support the opinion that the phenylboronic acid groups in the copolymers are responsible for the specific induction of tissue formation of BAECs through the interaction with glycoconjugates on the cell membranes.

本研究では, 固体表面に修飾したポリ (N-イソプロピルアクリルアミド) (PIPAAm) の構築構造が温度に応答したぬれ特性, ステロイドとの相互作用に与える影響を検討し, クロマト担体としての特性を追究した.PIPAAm共重合体を固体表面と多点で結合させた表面, さらにこの表面に片末端アミノ化PIPAAmを導入し自由末端鎖構造を有するグラフト表面をそれぞれ作製した.PIPAAm導入表面は温度に応答して親水性/疎水性の変化を示すが, その挙動は2つの表面で大きく異なっていた.自由末端鎖導入表面はPIPAAm分子が水中で示す相転移温度 (305K) で大きな変化を示したが, 多点で結合した表面ではより低温側になった.この表面特性の相違は, ステロイドとの相互作用にも認められ, 自由末端鎖導入表面は高温側でより強い疎水性相互作用を示すことが明らかとなった.温度上昇にしたがい表面の疎水性は次第に増大し, ステロイドの溶離時間を大幅に延長することができた.修飾高分子の構築構造制御により溶質との相互作用を変化できる新しいクロマト担体を実現した.

Micelles of poly(ethylene oxide)-block-poly(β-benzyl- l -aspartate) (PEO-PBLA) were loaded with doxorubicin (DOX) and were characterized in relation to their use as drug vehicles. First, an oil-in-water emulsion method was developed to load DOX in PEO-PBLA micelles. The level of DOX in PEO-PBLA micelles was 5–12% w/w. Whereas the mean diameter of unloaded, PEO-PBLA micelles was ca., 19 nm, the mean diameter of PEO-PBLA micelles loaded with DOX was ≈37 nm. Minimal chemical degradation of DOX occurred as a result of loading in PEO-PBLA micelles. In addition, DOX in PEO-PBLA micelles was less susceptible to chemical degradation than free DOX in aqueous solution. There was evidence for retention of DOX in PEO-PBLA micelles even after freeze-drying and reconstitution in water. Lastly, PEO-PBLA micelles served as drug depots, slowly releasing DOX (days), even in the presence of 10% w/v serum albumin. The results suggest a number of pharmaceutical advantages of PEO-PBLA micelles for the delivery of DOX.

The success of most advanced drug delivery strategies requires development of sophisticated new site-specific carriers. Several new targeting methods use physical and chemical signals such as magnetic fields or changes in pH or temperature as targeting and triggering tools. In addition to site-specificity, the carrier should achieve passive targeting to evade the body's reticulo-endothelial system (RES) and exhibit long blood circulation times in order to efficiently distribute active drug to the site of action (active targeting). To fulfil these requirements, thermo-responsive polymeric micelles have been prepared from amphiphilic block copolymers composed of N -isopropylacrylamide (IPAAm) (a thermo-responsive outer shell) and styrene (St) (hydrophobic inner core). The polymeric micelle which is very stable in aqueous media was formed by the dialyzed method from DMF solution against water. The micelles have a unimodal size distribution (24±4 nm) and CMC was around 10 mg/l (ml→l). These micelles have a small diameter with a low critical micelle concentration, providing a carrier that may have long blood circulation times and a low RES uptake. When the temperature is increased above the transition temperature of the thermo-responsive block chains (32°C), the outer shell chains dehydrate and collapse, allowing aggregation between micelles and favoring binding interactions with cell membrane surfaces. Moreover, these changes are reversible. Hydrophobic molecules are shown to be incorporated into the inner hydrophobic core of the thermo-responsive micelles. Consequently, these micelles are valuable for site-specific delivery of drugs using changes in temperature as a trigger.

Sodium alginate forms a hydrogel upon contact with calcium ions in aqueous solution due to the physical crosslinking (chelation) between the carboxylate anions of guluronate units in alginate and the calcium ions. Alginate disintegration (dissolution) in phosphate buffered saline solution (pH 7.4, Ca 2+ -, Mg 2+ -free) occurs completely in a short time period after a certain lag time. Calcium ion release from the alginate gels is believed to be an influential factor in alginate dissolution. Using this alginate dissolution mechanism, we tried to release macromolecular dextran (nominal molecular weight of 145 000) in a pulsatile manner. As was expected, dextran with molecular weight of 145 000 was released completely in a short time range after a certain lag time. The lag time could be controlled by either alginate molecular weight, alginate concentration in the preparation, or gel beads size. The larger the diameter of the alginate gel beads, the later the observed release time onset. Thereafter dextran was released without changing release rate. Furthermore, we have succeeded to release dextran in a pulsatile fashion using calcium-alginate gel beads by mixing different bead sizes. These results indicate that pulsatile release of macromolecular drugs such as peptides and proteins could be achieved using calcium-alginate gel beads.

Alkyl-terminated PIPAAm was obtained by covalent coupling of alkyl groups of different chain lenghts (C3, C6, C8, C12 and C18) to one end of poly(N-isopropylacrylamide) (PIPAAm). At the molecular level, incorporation of the alkyl chains with PIPAAm chains promoted aggregation at temperatures below the LCST (lower critical solution temperature) of pure PIPAAm, reflecting the hydrophobic contribution of the alkyl chains to the LCST. The LCST changes were greatest for stearoyl (C18)-terminated PIPAAm (PIPAAm-C18H35). Interestingly, this polymer above its critical micelle concentration (cmc, 80 mg/L) in aqueous solution had the same LCST as unmodified PIPAAm, owing to formation of a core-shell micellar structure shielding the hydrophobic inner alkyl core from interactions with water. Micelle formation and the micellar structure of the alkyl-terminated PIPAAm aqueous dispersions were analyzed by fluorescence, surface tension and DLS (dynamic light scattering) measurements. Micelle formation is facilitated by both an increase in hydrophobicity of the incorporated group and suppression of PIPAAm hydrophilicity upon heating, closely relating to intramolecular hydrophilic/hydrophobic balance. PIPAAm-C18H35 micelles exhibit two heterogeneous microdomains; a hydrophobic inner core highly capable of solubilizing hydrophobic pyrene molecules, plus a hydrated outer shell that stabilizes this micellar structure below its LCST and shows reversible thermoresponsive aggregation/dispersion in heating/cooling thermal cycles through the LCST.