The important factors that influence the progress of ischemic cardiac lesion are blood flow condition and abnormal cardiac metabolism. Myocardial ischemia is promoted by either an increase in oxygen demand or a shortage of oxygen supply. The Na⁺-Ca⁺⁺ ion exchange mechanism is very important for myocardial contraction and cell damage. Na⁺-K⁺ATPase and Ca⁺⁺ATPase are enzyme histochemically localized in subsarcolemmal cisterns, sarcolemmal reticulum and capillary endothelium, and keep myocardial function. These ATPases are impaired by anoxia, superoxides and free radicals. The reduction of O₂ results in the production of superoxides as well as hydrogen peroxide (H₂O₂). H₂O₂ is highly diffusible and induces cell damage. H₂O₂ appears to affect not only lipids but also intramembranous proteins embedded in the cell membrane. The hydroxyl radical (OH) also participates in lipid hyperoxidation. In the pathogenesis of ischemic and/or reperfused heart disease, ischemia induces rapid or gradual changes in all membrane systems and causes reversible or irreversible injury including necrotic and apoptotic cell death. Advanced glycation end products (AGEs) accumulation induced by diabetic conditioning is an etiologic factor inducing cardiomyopathy. The AGEs protein affects cell changes such as increased number, transformation, functional disturbance and cytokine elimination. In coronary arteries, the migration of smooth muscle cells caused by the taking up of AGEs proteins through the receptor (RAGE), and cytokine discharge are suggested. AGEs accumulation may induce diabetic macroangiopathy through RAGE, and the increase in the level of RAGE expression by endothelial cells could be a reason that diabetes mellitus accelerates atherosclerosis. On the other hand, we also reported that hyperglycemia was a promoting factor of ischemic heart injury in diabetic animals. Ischemic preconditioning is a useful phenomenon that limits myocardial damage. We foused on protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and mitochondrial ATP-dependent potassium (mitoK_ATP) channel as mediator or end which effector are necessary for adaptation. The opening of the mitoK_ATP channel induces the depolarization of mitochondria, reducing Ca⁺⁺overload during reperfusion. The regeneration of myocardial cells is confirmed using embryonic stem cells. Myocardial cells that exhibit self-pulsation are generated from mesenchymal stem cells in mesodermal tissues of the bone marrow.

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The Milligan-Morgan (MM) operation is the most widely practiced procedure for prolapsed hemorrhoids. But it is also associated with a fair amount of postoperative pain, a long period of convalescence, and complications like bleeding and anal stenosis. The aim of this study was to evaluate the efficacy of in-situ radiofrequency ablation (RA) of hemorrhoids.During a 6-month period, 40 patients with grade 3 hemorrhoids were prospectively randomized for RA (21 patients) or MM hemorrhoidectomy (19 patients). Patients were evaluated for operative time, postoperative pain, time to return to work and occurrence of early and late complications.Duration of surgery was significantly higher in the MM group (p<0.0001). Postoperative hospitalization was longer in the MM group (p<0.001). The post defecation pain and pain at rest were much less in the RA group (p<0.001). Wound healing period (16.3 vs. 37.5 days) and time to return to work (7.3 vs. 18.3 days) were other significant findings. Early complications occurred more frequently in the MM group, but late complications like external skin tags [4 patients vs. 2 patients] and one asymptomatic recurrence was noted in the RA group.In-situ RA of prolapsing hemorrhoids is a quick and bloodless procedure. It is associated with significantly less postoperative pain, shorter hospital stay and early return to normal activity. It can be considered as an alternative to conventional hemorrhoidectomy.

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Mucoepidermoid carcinoma of the esophagus (MEC) is uncommon and has not been fully investigated. The biological behavior and clinical aspects of MEC were studied.The clinical features of eight patients with MEC were compared with 51 cases of squamous cell carcinoma of the esophagus (SCC). Proliferating cell nuclear antigen (PCNA), p53, and carcinoembryonic antigen (CEA) were stained in the resected specimens by immunohistochemistry.Seven out of 8 cases (87.5%) had stage III by TNM classification. Four cases died of widespread metastases and 2 cases died of local recurrence within 2 years after the surgery. Neither chemotherapy and radiotherapy were effective against MEC. Overall median survival periods were 10.8 months for MEC and 32.1 months for SCC (P<0.05). When patients in stage III alone were compared, MEC tended to have a worse prognosis than SCC (P=0.058). Immunohistochemical studies revealed that the positive rates of PCNA and CEA were significantly higher in MEC than in SCC (P<0.05), while there was no significant difference in p53 positive rate.Esophageal MEC had an aggressive biological nature and was resistant to adjuvant therapies. The poor prognosis of esophageal MEC may be caused by high proliferative and metastatic potential.

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Mitochondria (mt) have been reported to be closely related to the maturation of mammalian oocytes, but their function in oocyte maturation has not been elucidated. In this study, we examined the kinetics of mt and chromatin configuration during in vitro maturation of mouse oocytes to clarify the relationship between oocyte maturation and mitochondrial distribution morphologically. Oocytes were recovered from 6-to 8-wk-old ICR strain female mice. Germinal vesicle (GV) -stage oocytes were divided into 4 groups and cultured: group A, oocytes collected after pregnant mare serum gonadotropin (PMSG) injection; and group B, oocytes collected after PMSG-human chorionic gonadotropin injection. Groups A and B were subdivided into 2 groups: denuded oocytes (DO) and cumulus-enclosed-oocytes (CEO). At 0, 4, 8, 12 and 16 h from the onset of the culture, oocytes were fixed and stained to visualize α-tubulin, chromatin and mt using confocal laser scanning microscopy (CLSM). It was observed that mt aggregated around the nucleus from the GV-stage through progression to germinal vesicle breakdown (GVBD). With the movement of the nucleus, mt were concentrated around the nucleus and polarized. The maturation rate (the rate of the first polar body extrusion) and the fertilization rate of CEO were significantly higher than that of DO in both groups A (p<0.01) and B (p<0.05). During the GV-stage to GVBD, the rate of mitochondrial aggregation around the nucleus tended to be high in group A (CEO). The rates of mitochondrial polarization in MI and MII oocytes were 76.1% with in-vitro maturation (IVM) and 86.7% with in-vivo-maturation, respectively; the rate was significantly higher in in-vivo-maturation-oocytes than in IVM-oocytes (p<0.01). From the present results it can be considered that aggregaton of mitochondria around the nucleus was essential for maturation, fertilization and development.

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Purpose: To study the relationship of angles in adult sacroiliac joints (SJ) with laterality, age, gender, degeneration, childbearing in different locations.Methods: The study was performed in 92 healthy Japanese adult volunteers (46 males and 46 females, aged 21∼86 years) who had no low back complaints. Axial computed tomographic (CT) images were obtained using an X-VIGOR apparatus (Toshiba Medical Inc. Japan). The angle measurements were taken directly using soft NIH Image 1.61 (Scion Inc. USA). We examined possible factors. Statistical evaluation was calculated using t-test by soft SPSS (SPSS Inc. Japan).Results: Our findings indicated that SJ angles had no relationships with laterality, gender. But from upper part to lower part, the average of SJ angle was 7.61°±8.7°, 5.16°±7.3°, -0.85°±7.3°respectively in the left and 6.56°±9.4°, 4.10°±7.2°, -2.30°±7.0°in the right. The difference is significant between lower part and upper-middle part (P<0.05).Conclusion: Our results provided new anatomic and morphological data for better understandings of SJ in the clinic work.

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The stem cells are promising for future cell-based therapy such as tissue engineering or regenerative medicine. Although Embryonic Stem Cells (ESCs) are theoretically highly beneficial, there are various limitations on their use posed by cell regulations and ethical considerations. Therefore, adult stem cells are considered to be highly available with neither ethical nor immunoreactive considerations as long as they are of autologous tissue origin. Much of work has focused on the Mesenchymal Stem Cells (MSCs) isolated from bone marrow stroma, which have been shown to possess adipogenic, osteogenic, chondrogenic, myogenic and neurogenic potential in vitro. However bone marrow procurement is severely painful for patients and the harvested cells yields low number.Our preliminary studies have identified a putative stem cell population isolated from human adipose tissue. This cell population, termed Processed Lipoaspirate Cells (PLA Cells), is found to differentiate into adipogenic, osteogenic, chondrogenic and myogenic lineage in vitro in lineage-specific culture media. In addition to these findings, our recent data shows that PLA cells can be induced to differentiate into neural precursors, which are of an ectodermal origin. Furthermore, PLA cells express multiple CD marker antigens similar to those observed on MSCs. Finally, some of PLA clonal cells have capabilities of differentiate into adipogenic, osteogenic and chondrogenic lineage. These findings suggest that human PLA have a mesodermal stem cell population. Since human adipose tissue is ubiquitous, easily obtainable in large quantity under local anesthesia with little patient discomfort, it may be an alternative stem cell source for mesenchymal tissue regeneration and engineering.

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A powerful artificial anti-apoptotic factor will be useful for the reproductive therapies for many diseases by prolonging survival of stem cells. For constructing it, we designed the super anti-apoptotic factor by disturbing three intramolecular polar interactions among α-helix structures of Bcl-xL. The resultant mutant Bcl-xL, named FNK, was expected to make the pore-forming domain more mobile and flexible than the wild-type. When overexpressed in Jurkat cells, FNK was markedly more potent in prolonging survival following apoptosis-inducing treatment with a kind of cell death cytokines (anti-Fas), a protein kinase inhibitor (staurosporine), cell cycle inhibitors (TN-16, camptothecin, hydroxyurea and trichostatin A) or oxidative stress (hydrogen peroxide and paraquat) than wild-type Bcl-xL. Furthermore, the transfectants of FNK became more resistant against a calcium ionophore and even a heat treatment than wild-type Bcl-xL. In addition, FNK showed marked anti-apoptotic activity in CHO and Jurkat cells deprived of serum. Thus, FNK may be the first mutant generated by site-directed mutagenesis of Bcl-xL with an enhance gain-of-function phenotype.Next, we tried to transduce the FNK protein into cells. Protein therapeutics has the advantage of delivering proteins in a short period of time. We have engineered the anti-apoptotic bcl-x gene to generate the super anti-apoptotic factor, FNK, with a more powerful cytoprotective activity. In this study, we fused the protein transduction domain (PTD) of the HIV/Tat protein to FNK, and used the construct in an animal model of ischemic brain injury. When added into culture media of human neuroblastoma cells and rat neocortical neurons, PTD-FNK rapidly transduced into cells and localized to mitochondria within 1 hr. It protected the neuroblastomas and neurons against staurosporine-induced apoptosis and glutamate-induced excitotoxicity, respectively. The cytoprotective activity of PTD-FNK was found at concentrations as low as 0.3 pM. Additionally, PTD-FNK affected the cytosolic movement of calcium ions, which may relate to its neuroprotective action. Immunohistochemical analysis revealed that myc-tagged PTD-FNK (PTD-myc-FNK) injected intraperitoneally into mice can have access into brain neurons. When injected intraperitoneally into gerbils, PTD-FNK prevented delayed neuronal death in the hippocampus caused by transient global ischemia. These results suggest that PTD-FNK has a potential for clinical utility as a novel protein therapeutic strategy to prevent cell death in the brain.Thus, the protein delivery system will be useful to make cells survived for a long time during the differentiation of stem cells in the reproductive therapies.

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We present here a case of maternal reaction to fetomaternal transfusion complicated by subchorionic hemorrhage. A 40-year-old woman, gravida 2, para 0, was admitted to our hospital at 25 weeks' gestation because of high blood pressure. On the morning of 32 weeks and 2 days' gestation, she developed sudden onset nausea, dyspnea and regular uterine contractions. Blood pressure was 80/50 mmHg and pulse was 110 beats/minute. At this time, her WBC, hemoglobin and platelets were decreased significantly. Two hours after onset, the patient's condition improved spontaneously. Increased serum alpha-fetoprotein level (3.0 multiple of median) was observed. She was suggested to be a case of acute fetomaternal transfusion.

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We present here a case of uterine perforation following manual removal of the placenta during the third stage of normal labor. Total abdominal hysterectomy was performed, and the 4×3-cm perforation of the uterus and placenta accreta were confirmed. In this case, the round ligament covering the hematoma prevented bleeding into the peritoneal cavity and peritonitis. Manual removal of the placenta should be performed carefully following ultrasonographic assessment for placental abnormalities such as placenta accreta.

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A 74-year-old woman visited her local physician complaining of fever, cough, headache, hyperemic left conjunctiva, and blurred vision. She was diagnosed as having common cold and medicated for it, and later, she visited our department. She had a shallow left anterior chamber with moderately dilated pupil. Gonioscopic examination of the left eye revealed a narrow angle corresponding to grade 1 by Shaffer grading system. Left intraocular pressure was 16 mmHg. She was diagnosed to have had a spontaneous recovery from a subacute attack of angle-closure glaucoma. Laser iridectomy was performed and she was put on a regular ophthalmological follow-up. Three years later, she experienced an attack of left angle-closure glaucoma secondary to lens intumescence. She was treated by phacoemulsification and aspitaion which resulted in the eventual cure.

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