Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions

Gene therapy is expected to open a new strategy for the treatment of refractory vascular diseases, so the development of appropriate gene vectors for vascular lesions is needed. To realize this requirement with a non-viral approach, cyclo(RGDfK) peptide (cRGD) was introduced to block copolymer, poly(ethylene glycol)-block-polycation carrying ethylenediamine units (PEG-PAsp(DET)). cRGD recognizes αvβ3 and αvβ5 integrins, which are abundantly expressed in vascular lesions. cRGD-conjugated PEG-PAsp(DET) (cRGD-PEG-PAsp(DET)) formed polyplex micelles through complexation with plasmid DNA (pDNA), and the cRGD-PEG-PAsp(DET) micelles achieved significantly more efficient gene expression and cellular uptake as compared with PEG-PAsp(DET) micelles in endothelial cells and vascular smooth muscle cells. Intracellular tracking of pDNA showed that cRGD-PEG-PAsp(DET) micelles were internalized via caveolae-mediated endocytosis, which is associated with a pathway avoiding lysosomal degradation, and that PEG-PAsp(DET) micelles were transported to acidic endosomes and lysosomes via clathrin-mediated endocytosis. Further, in vivo evaluation in rat carotid artery with a neointimal lesion revealed that cRGD-PEG-PAsp(DET) micelles realized sustained gene expression, while PEG-PAsp(DET) micelles facilitated rapid but transient gene expression. These findings suggest that introduction of cRGD to polyplex micelles might create novel and useful functions for gene transfer and contribute to the establishment of efficient gene therapy for vascular diseases

Characteristics of breast cancer support groups within hospitals in Japan

施設内の乳がん患者会の有無とその特徴を明らかにする目的で,日本乳癌学会参加564施設(認定347施設,非認定217施設)を対象に郵送質問紙調査を行った.236施設(回収率41.8%)から回答があり,以下の結果を得た.1)乳がん患者会がある施設は,236施設中52施設(22.0%)であった.2)乳がん患者会がある施設の設置主体,規模及び日本乳癌学会認定の有無に違いは見られなかった.しかし,年間乳がん手術件数は,患者会がある施設が有意に多かった.3)患者会は,医療者が発起している会が52施設中22施設(42.3%),患者が発起している会が17施設(32.7%),患者と医療者で発起している会が8施設(15.4%)であった.施設内の患者会は,医療者と患者がコミュニケーションを図る場所,退院直後や外来で活発な治療を受けている時期の患者にとっては利用しやすい身近なサポート資源であると考えられた.4)施設内の患者会は会の内容,運営など,医療者主導の会が多く,セルフヘルプ性は低かった.また,患者の年齢,術後年数など幅があるため,患者個々のニーズには対応できない部分もあり,術後経過と共に支援の内容や必要性が変化してきた際には,施設外の患者会も利用していくシステムも今後必要ではないかと示唆された.The purpose of this study was to determine the number of breast cancer support groups withinhospitals and to describe their characteristics. A questionnaire was mailed to 564 member hospitals of theJapanese Breast Cancer Society (347 accredited, 217 non-accredited). 236 hospitals responded (a responserate of 41.8 percent), and we obtained the following results.1) 52 of 236 hospitals (22.0 percent) had a breast cancer support group.2) No significant differences were found among the hospitals concerning their administrative entity, size,or accredited versus non-accredited status by the Japanese Breast Cancer Society. However, thehospitals with a support group performed a significantly larger number of breast cancer operationsannually than those without a group.3) 22 (42.3 percent), 17 (32.7 percent) and 8 (15.4 percent) of the 52 hospitals had a support groupestablished by physicians, patients, or by both physicians and patients, respectively. A support groupwithin a hospital is considered to provide opportunities for physicians and patients to communicate, aswell as a patient-friendly support resource for those who have just left the hospital and those who areunder intensive treatment on an outpatient basis.4) Many of the support groups were headed by physicians in content and administration and played arather small role as a self-help resource. Additionally, some support groups could not cover patients'individual needs because the ages and postoperative periods of patients varied widely. Therefore, it issuggested that a system be devised where patients can utilize outside support groups when the contentand requirements of needed support change during the postoperative period

Median nerve neuropathy in the forearm due to recurrence of anterior wrist ganglion that originates from the scaphotrapezial joint: Case Report

<p>Abstract</p> <p>Background</p> <p>Median nerve neuropathy caused by compression from a tumor in the forearm is rare. Cases with anterior wrist ganglion have high recurrence rates despite surgical treatment. Here, we report the recurrence of an anterior wrist ganglion that originated from the Scaphotrapezial joint due to incomplete resection and that caused median nerve neuropathy in the distal forearm.</p> <p>Case presentation</p> <p>A 47-year-old right-handed housewife noted the appearance of soft swelling on the volar aspect of her left distal forearm, and local resection surgery was performed twice at another hospital. One year after the last surgery, the swelling reappeared and was associated with numbness and pain in the radial volar aspect of the hand. Magnetic resonance imaging revealed that the multicystic lesion originated from the Scaphotrapezial joint and had expanded beyond the wrist. Exploration of the left median nerve showed that it was compressed by a large ovoid cystic lesion at the distal forearm near the proximal end of the carpal tunnel. We resected the cystic lesion to the Scaphotrapezial joint. Her symptoms disappeared 1 week after surgery, and complications or recurrent symptoms were absent 13 months after surgery.</p> <p>Conclusions</p> <p>A typical median nerve compression was caused by incomplete resection of an anterior wrist ganglion, which may have induced widening of the cyst. Cases with anterior wrist ganglion have high recurrence rates and require extra attention in their treatment.</p

A Case Report of Carcinoma Originating from Aberrant Breast Tissue

A case of breast cancer originating from accessory breast gland tissue is to be presented. Treatment included the subcutaneous removal of the upper half of the mammary gland and the dissection of axillary lymphnodes. As the incidence of aberrant breast carcinoma is rare, a definite prognostic conclusion can not be made at this point. But follow up (5 years) in our case without recurrence will prove that it is enough when the masses were not palpable within the breast

Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking

Background: Lymphocytes circulate between peripheral lymphoid tissues via blood and lymphatic systems, and chemokine-induced migration is important in trafficking lymphocytes to distant sites. The small GTPase Rap1 is important in mediating lymphocyte motility, and Rap1-GEFs are involved in chemokine-mediated Rap1 activation. Here, we describe the roles and mechanisms of Rap1-GEFs in lymphocyte trafficking. Results: In this study, we show that RA-GEF-1 and 2 (also known as Rapgef2 and 6) are key guanine nucleotide exchange factors (GEF) for Rap1 in lymphocyte trafficking. Mice harboring T cell-specific knockouts of Rapgef2/6 demonstrate defective homing and egress of T cells. Sphingosine-1-phosphate (S1P) as well as chemokines activates Rap1 in a RA-GEF-1/2-dependent manner, and their deficiency in T cells impairs Mst1 phosphorylation, cell polarization, and chemotaxis toward S1P gradient. On the other hand, B cell-specific knockouts of Rapgef2/6 impair chemokine-dependent retention of B cells in the bone marrow and passively facilitate egress. Phospholipase D2-dependent production of phosphatidic acid by these chemotactic factors determines spatial distribution of Rap1-GTP subsequent to membrane localization of RA-GEFs and induces the development of front membrane. On the other hand, basal de-phosphorylation of RA-GEFs is necessary for chemotactic factor-dependent increase in GEF activity for Rap1. Conclusions: We demonstrate here that subcellular distribution and activation of RA-GEFs are key factors for a directional movement of lymphocytes and that phosphatidic acid is critical for membrane translocation of RA-GEFs with chemokine stimulation

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m(3) and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m(3)) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m(3)) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m(3) thoron inhalation was lower than that after 500 Bq/m(3) thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m(3) and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m(3) was more effective than that at 2000 Bq/m(3), possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m(3) and AA administration promoted an early recovery from alcohol-induced liver damage

Formation, Thermal Stability and Mossbauer Effect of Amorphous, Quasicrystalline and Crystalline Phases in Al-(Cu, Ni)-Fe Systems

Nonequilibrium phase including amorphous and bcc phases in Al-Cu-Fe and Al-Ni-Fe systems formed by sputtering method. The composition range of the formation phases are determined, in harmony with that of the binary Al-transition system. The composition range (Ni=10～15 at%, Fe=10～15 at%) of melt-quenched quasicrystalline phase is the formation region of an amorphous phase in a vapor quenched state. In the investigation for Al_Ni_Fe_ alloy, two exothermic peaks in calorimetric curves are observed during heating. The first peak is correlated with the precipitation of bcc-like nanocrystalline from vapor-quenched amorphous matrix, and the second peak is due to formation of decagonal phase. The Mossbauer spectra of these vapor-quenched nonequilibrium phases are examined and it is concluded that the local structure around Fe atom is similar among icosahedral, decagonal, amorphous and bcc phases