Correction of cryptotia using a subcutaneous pedicled flap

Cryptotia is a relatively common deformity of the ear among orientals. Although many methods for correcting this deformity have been reported, there is no one perfect method. We have developed a method using a subcutaneous pedicle flap raised from the retroauricular region, where relative abundance of skin exists. We have treated 9 ears of 7 patients by the method reported herein. Results are satisfactory in all cases.     

Latero-lateral end anastomosis for right hemicolectomy using staplers

In seven patients undergoing right hemicolectomy for benign or malignant diseases, latero-lateral end anastomoses were made using stapling devices, LS (linear stapler) and GIA (gastrointestinal anastomosis). As no complications directly related to the anastomosis occurred, we conclude that anastomosis using stapling devices for right hemicolectomy is a safe and rapid procedure.     

Operation for polysyndactyly of the fifth toe using Z-plasty.

A new operative procedure was devised to treat polysyndactyly of the fifth toe. This procedure, which consists of removal of the fifth toe, correction of the alignment of the preserved sixth toe by arthroplasty and construction of an interdigital space by Z-plasty, is technically simple and produces good results, both functionally and aesthetically.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Regulation of the small GTPase RhoA by syndecan-4 and integrins in focal adhesion formation

Introduction The transmembrane heparan sulfate proteoglycan, syndecan‐4, and integrins are important receptors for focal adhesion (FA) formation on fibronectin (FN) substrates. The small GTPase RhoA is also known to regulate FA and stress fiber formation. It has been suggested that syndecan‐4 and integrins co‐operatively regulate the assembly of FA in a Rho‐dependent manner, but the mechanism is unclear. Here, we examined the function of RhoA and the Rho effector kinases ROCKs in syndecan‐4 signalling on the process of FA formation and the possible mechanism by which syndecan‐4 may regulate RhoA activity. Methods Primary rat embryonic fibroblasts (REFs) were seeded on FN or ‘RGD’‐containing integrin‐binding domain of FN and lysed at various time points. The amount of active form of RhoA in each lysate was analysed by pull‐down experiments. Results and discussion The relative activities of RhoA showed one peak in the process of FA formation on FN, whereas no peak was obtained on the integrin‐binding domain. The one peak of RhoA activity on integrin‐binding domain was restored by addition of heparin‐binding domain into medium. These results suggested that a signal through syndecan‐4 link to the Rho pathway. Both ROCK‐I and ‐II isozymes were present in REF cell lysates and each could be specifically immunoprecipitated. The ROCK kinase activities in immunoprecipitates were analysed using GST‐myosin light chain as a substrate. The amount of ROCK‐I and ‐II activities changed through the adhesion process on FN and appeared to be independently regulated. Therefore, one or both ROCKs may be downstream of a syndecan‐4‐mediated signalling response through RhoA. The core protein of syndecan‐4 can directly bind to and activate PKC‐α. We found that PKC‐α could phosphorylate Rho‐Guanine Nucleotide Dissociation Inhibitor (GDI) in vitro. It has been suggested that PKC‐α‐mediated phosphorylation of Rho GDI stimulates GDI dissociation, thereby resulting in Rho activation. It is possible that syndecan‐4 regulates Rho/ROCK pathway through PKC‐α activation on the process of FA formation.     

Influence of fibroblasts on the invasion and migration of highly or weakly metastatic b16 melanoma cells

We have examined the influence of fibroblasts on the invasive and migratory potential of highly metastatic melanoma B16-BL6 and weakly metastatic B16-FI cells in vitro. Co-culture of B16-BL6 cells with a fibroblast monolayer without cellular contact in a Transwell chamber more effectively induced tumor-cell invasion into Matrigel basement membrane than co-culture of B16-FI cells with a fibroblast monolayer. The activity was closely correlated with the chemotactic migration of tumor cells toward the fibroblast monolayer. We also found that the conditioned medium (CM) from the co-culture of fibroblasts with B16-BL6 cells without cellular contact, i.e., CM (B16-BL6/fibroblast), rather than from co-culture with B16-FI cells, could potentially promote the migration of tumor cells of both types. Tumor cells did not chemotactically migrate to the CM (B16-BL6), CM (B16-FI) or CM (fibroblast). Antibodies against TGF-β1 or FN almost completely abolished the chemotactic migration of B16-BL6 cells to the CM (B16-BL6/fibroblast) or CM (TGF-β1 -treated fibroblast) when these antibodies were c-incubated with fibroblasts and either B16-BL6 or TGF-β1. In contrast, the anti-EGF antibody did not show any inhibitory effects. Analysis of amounts of TGF-β1 or FN in various CM using ELISA plates, and using their specific antibodies, revealed that the concentration of TGF-β1 in the CM (B16-BL6) was slightly higher than in the CM (B16-FI), and the amount of FN in the CM (B16-BL6/fibroblast) was twice as high as in the CM (B16-FI /fibroblast). These results suggest that TGF-β1 released from B16-BL6 cells can stimulate fibroblasts to produce FN; consequently, the tumor cells were able to chemotactically migrate toward the released FN, and the differences in invasive and migratory activities towards fibroblasts in B16-BL6 and B16-FI cells may in part be due to the amounts of TGF-β1 from tumor cells and of FN from TGF-β1 -stimulated fibroblasts.     

Surgical strategies for treatment of giant or large intracranial aneurysms: our experience with 139 cases.

Giant or large intracranial aneurysms are the vascular neurosurgeon's greatest challenge. At our department, we have treated one hundred and thirty nine patients with giant or large intracranial aneurysms between 1975 and 2001. These included 37 partially thrombosed giant aneurysms. 75 aneurysms were giant (> 2.5 cm) and 64 were large aneurysms (2-2.5 cm). Three-dimensional computed tomography angiograms were performed in patients besides MRI angiography and digital subtraction angiography. These were found to be very valuable in the preoperative assessment of surgical anatomy of the aneurysm with respect to the branch arteries and perforators origin besides knowing the relations to the skull base. With our experience in surgical treatment of these 139 cases, we find that the basic technique is trapping and evacuation and not just clipping of the aneurysm neck but also reconstruction of the artery bearing the aneurysm, especially with wide-necked aneurysms. Use of multiple clipping, tandem clipping or dome clipping as per the intraoperative situation, is very helpful in dealing with giant aneurysms as also is the use of different types of clips like fenestrated clip with straight clip (combination clipping), booster clip, dome clips etc. While selecting surgical strategy for partially thrombosed giant aneurysm, securing the neck is most important. If the neck is too narrow to reconstruct, aneurysmectomy with anastomosis is one of the surgical strategies. An extracranial intracranial bypass should be considered in cases where clipping or parent artery ligation is expected to be associated with compromise of cerebral circulation.     

Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).