Omental liposarcoma; a rare complication in neurofibromatosis type 1.
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Female↗
Biomedical subjects
T Kurokawa
Publications and source records attributed to T Kurokawa.
DARPP-32 expression arises after a phase of dysplasia in oesophageal squamous cell carcinoma.
This is the first report to correlate DARPP-32 immunoreactivity (dopamine and cAMP-regulated phosphoprotein, M(r) 32 000) to clinicopathological status in human cancer. DARPP-32 is recognised as a neuronal protein. A recent study demonstrated that DARPP-32, and a truncated isoform t-DARPP, are overexpressed in gastric carcinoma during the process of carcinogenesis. The biological function of DARPP-32, however, is still unclear. The purpose of this study was to clarify the roles of DARPP-32 and t-DARPP in oesophageal squamous cell carcinoma (OSCC). Initially, we investigated DARPP-32 and t-DARPP expression in OSCC cell lines by Reverse transcription-polymerase chain reaction and Western blot. DARPP-32 expression was observed in four out of seven (57.1%) cell lines, but t-DARPP expression was not observed in any cell lines. In oesophageal tissue sample, DARPP-32 expression was observed in four out of seven (57.1%) tumour tissues, while t-DARPP was not observed in any tissues. Subsequently, DARPP expression was assessed by immunohistochemistry, using a polyclonal antibody, in tissue sections from 122 patients with primary OSCC. DARPP immunoreactivity was not observed in any normal oesophageal mucous membranes. On the other hand, positive DARPP immunostaining was detected in 37 patients (30.3%) and correlated inversely with pathologic stage (P=0.0284), pT (P=0.0438), pN (P=0.0303) and tumour size (P=0.012). The overall survival rate was worse in patients with DARPP-negative tumours than in patients with DARPP-positive tumours (P=0.0453). Interestingly, DARPP expression was observed in only one out of 45 cases of dysplasia. These observations suggest that DARPP-32 (rather than t-DARPP) expression arises after a phase of dysplasia in OSCC, and that tumours expressing DARPP-32 progress less rapidly than DARPP-32-negative tumours.
Adult↗
Fusion of HIV-1 Tat protein transduction domain to poly-lysine as a new DNA delivery tool.
Effective gene therapy depends on the efficient transfer of therapeutic genes to target cells. None of the current technologies, however, satisfy all of the requirements necessary for gene therapy, because the plasma and nuclear membranes of mammalian cells are tight barriers against gene transfer using synthetic delivery systems. The protein transduction domain (PTD) of human immunodeficiency virus type 1 (HIV-1) Tat protein greatly facilitates protein transfer via membrane destabilisation. We synthesised polylysine peptides containing Tat PTD (TAT-pK), or other sequences, and investigated their potential as agents for gene transfer. The synthesised polypeptide TAT-pK retains DNA binding function and mediates delivery of a reporter gene to cultured cells. RGD motif binds with low affinity to alpha integrins which induce cell activation. Two control polypeptides, GGG-pK and RGD-pK, were synthesised and tested, but their gene transfer abilities were weaker than those of TAT-pK. TAT-pK-mediated gene transfer was enhanced in the presence of chloroquine or ammonium chloride, to a greater extent than that of cationic lipid-mediated gene transfer in most cancer cell lines tested. These data suggest that TAT-pK may be a potent candidate delivery vehicle that promotes gene transfer, dependent on the endocytic pathway. We conclude that the TAT-pK/DNA complex is useful as a minimal unit to package therapeutic genes and to transduce them into mammalian cells.
Carcinoma↗
Angle closure glaucoma after laser photocoagulation for retinopathy of prematurity.
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Anterior Eye Segment↗
Overexpression of hypoxia-inducible-factor 1alpha(HIF-1alpha) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage.
The purpose of this study is to investigate the clinical and histopathologic significance of hypoxia-inducible-factor 1alpha (HIF-1alpha) expression in oesophageal squamous cell carcinoma. One hundred and thirty surgically resected specimens of OSCC were immunohistochemically assessed for HIF-1alpha expression with monoclonal antibody. High HIF-1alpha immunostaining was detected in 40 specimens. The percentage of high HIF-1alpha expression cases increased with tumour stage according to pTNM system. High HIF-1alpha expression correlated with pTNM stage, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion and positive surgical margin. The overall survival rate was worse in patients with high HIF-1alpha pattern than in patients with low-expression pattern. Univariate analyses identified high HIF-1alpha positivity, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion, and a positive surgical margin as risk factors. Multivariate analyses indicated that depth of tumour invasion, lymph node metastasis and positive surgical margin, but not HIF-1alpha, were independent prognostic factors. Survival in patients with a high HIF-1alpha expression was significantly worse than in those with low expression in patient treated with adjuvant therapy.
Adult↗
Caveolin-I overexpression is a favourable prognostic factor for patients with extrahepatic bile duct carcinoma.
Extrahepatic bile duct carcinoma (EBDC) is a malignancy well known for its poor prognosis. Some clinicopathological prognostic markers have been proposed, but genetic factors have not been well investigated. We have examined expression patterns of caveolin-1, which has been shown to function as a tumour suppressor in vitro, in EBDC using immunohistochemistry. Normal tissues adjacent to the tumour cells did not show immunoreactivity for caveolin-1. A total of 22 of the 60-carcinoma tissue samples (36.7%) studied were positive for caveolin-1. Caveolin-1 immunostaining negatively correlated with the patient's age and pathological T factor (pT) in a statistically significant manner. Multivariate analysis using Cox's proportional hazards model identified caveolin-1 expression as an independent positive prognostic factor. Thus, our study suggests that caveolin-1 expression may be a useful prognostic marker for EBDC.
Adult↗
Suppression of allergic reaction by lambda-carrageenan: toll-like receptor 4/MyD88-dependent and -independent modulation of immunity.
BACKGROUND: Recognition of foreign substances by innate immunity through pattern recognition receptors (PRRs) regulates acquired immunity such as allergic reaction. Because PRRs recognize heterogeneous ligands, daily food intake can potentially regulate immune allergic reaction. OBJECTIVE: Elucidation of the effect of lambda-carrageenan on allergic reactions was aimed. METHOD: IFN-gamma and IL-4 was measured in in vitro T cell-stimulated culture. Cytokine production from macrophages in response to lambda-carrageenan was measured as indicator for innate immunity activation. Mice were immunized with OVA in alum to induce specific IgE, and then histamine release was induced by systemic injection of OVA. RESULTS: Activation of innate immunity by lambda-carrageenan is dependent on Toll-like receptor-4 (TLR4) and MyD88, in which induction of pro-inflammatory cytokines such as TNF-alpha and IL-6 was largely impaired in macrophages from TLR4- and MyD88-deficient mice. Footpad oedema, a model for in vivo inflammatory reactions, was significantly reduced in these mice. Similar to recent evidence showing a preference for the stimulation of Th1 via TLR/MyD88 signalling, lambda-carrageenan showed enhanced IFN-gamma and decreased IL-4 in stimulated T cell cultures. Interestingly, increased IFN-gamma production was still seen in TLR4- and MyD88-deficient splenocytes. Oral administration of lambda-carrageenan to immunized mice successfully decreased OVA-specific IgE, and lambda-carrageenan was also effective in previously immunized mice. Further, serum histamine release upon systemic challenge of OVA was significantly inhibited. Neither OVA-specific IgG1/IgG2a nor cytokine secretion from in vitro cultures were altered, suggesting the involvement of multiple PRRs as demonstrated by TLR4/MyD88-independent IFN-gamma up-regulation. The simultaneous feeding of OVA with lipopolysaccharide abrogated oral tolerance, but lambda-carrageenan was not only devoid of such an effect but was also found to promote oral tolerance in the absence of TLR4. CONCLUSION: lambda-Carrageenan was suggested to be a useful dietary supplement to ameliorate allergic reactions while maintaining oral tolerance-dependent intestinal homeostasis.
Adaptor Proteins, Signal Transducing↗
Laparoscopic left hemihepatectomy combined with right hemicolectomy for liver tumor and hemorrhagic diverticulosis.
We report a case of laparoscopic left lobectomy combined with right hemicolectomy for cystic liver tumor and hemorrhagic diverticulosis of the ascending colon. Mobilization of the right hemicolon was performed first with a complete laparoscopic method. Then the surgeon's left hand was inserted into the abdominal cavity through a 75-mm incision made in the right upper quadrant, and the hand-assisted method was used for completion after liver resection. After hepatectomy, the right hemicolon was pulled through the hand port incision. The resection and anastomosis were performed extracorporeally to avoid intra abdominal infection. As a hemihepatic inflow control technique, we used the method of en masse occlusion of Glisson's sheath of the left hemipedicle at the bifurcation. The hand facilitates proper traction and exposure of the cut surface, and hemostasis can be achieved by proper application of vascular clips or staplers. The patient had an uneventful, rapid postoperative recovery.
Colectomy↗
Hand-assisted laparoscopic anatomical left lobectomy using hemihepatic vascular control technique.
We report a new approach for laparoscopic anatomical left lobectomy. Although laparoscopic limited resection of the liver has been reported, major liver surgery with a laparoscopic approach remains uncommon. Obstacles to routine laparoscopic surgery on the liver are mainly related to difficulty in retraction with current instrumentation, difficulty in assessing safe margins of resection without the use of tactile sense, and the difficulty of safe parenchymal dissection laparoscopically. We introduce a hand-assisted method that can help in resolving the difficulties and pitfalls associated with laparoscopic liver resection, and in making this surgery safer. The hand is the best atraumatic liver retractor in laparoscopic resection and facilitates the use of laparoscopic ultrasonography. Stable hemostasis can be achieved by proper manual application of vascular clips in case of vascular injury. The hemihepatic inflow control technique used in the present case was the en masse occlusion of Glisson's sheath of the left hemipedicle at the bifurcation. This technique was used exactly the same as in open surgery. Major vessels such as the left hemipedicle and left hepatic vein were dissected by endovascular cutter. The patient had an uneventful, quick postoperative recovery. This technique allows a minimally invasive anatomical major surgery for liver tumors.
Bile Ducts↗
Selective occlusion with fibrin glue under fistuloscopy: seven cases of postoperative management for intractable complex fistulas.
BACKGROUND AND STUDY AIM: Fistula occlusion is not achieved in some fistulas with complex branches. To obtain early fistula closure in such cases, we insert a double-lumen catheter into each fistula branch, with the aid of a guide wire positioned using a small-caliber endoscope, and attempt selective infusion of fibrin glue. PATIENTS AND METHODS: Following removal of foreign bodies and necrotic granulation, we applied the selective occlusion method under fistuloscopic control to seven intractable external fistulas with complex branches, in which fistula closure had not been obtained by a simple occlusion method (SOM). All the fistulas were complex with more than two branches. RESULTS: Fistula occlusion was obtained within 2 weeks in six of the seven patients, and there has been no sign of recurrence over a follow-up period of 4 - 59 months (average 29.8 months). CONCLUSION: Selective occlusion under fistuloscopy is highly effective for intractable external fistulas with complex branches.
Digestive System Surgical Procedures↗
Complement plays an important role in gastric mucosal damage induced by ischemia-reperfusion in rats.
Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress.
Animals↗
Metastin suppresses the motility and growth of CHO cells transfected with its receptor.
We recently reported having identified of the ligand for an orphan G-protein-coupled receptor, hOT7T175, as the gene product (68-121)-amide of the metastasis suppressor gene KiSS-1. We further showed that the ligand, which we named "metastin," inhibits chemotaxis and invasion of Chinese hamster ovary (CHO) cells transfected with hOT7T175 cDNA (CHO/h175) in vitro, and pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. In the present study, we investigated the activity of metastin in CHO/h175 cells in greater detail. Metastin significantly suppressed motility in a chemotaxis assay and wound healing assay at 10-100 nM order concentrations. Two N-terminally truncated peptides, metastin(40-54) and metastin(45-54) inhibited the migration of CHO/h175 cells as potently as metastin itself. Metastin also inhibited the spreading, monolayer growth and colony formation in agar (0.8%) of CHO/h175 cells at 10-100 nM concentrations. These results indicate that metastin is a potent inhibitor of cell motility, leading to suppression of cell growth and antimetastatic activity, and suggest that low molecular chemical compounds could replace its activity as a novel antimetastatic agent.
Animals↗
Cytotoxic T cell activity against the peptide, AYRARALEL, from Yo protein of patients with the HLA A24 or B27 supertype and paraneoplastic cerebellar degeneration.
OBJECTIVE: To determine a peptide that reacts with cytotoxic T cells (CTL) of patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies with either HLA A24 or B27 supertype. METHOD: We studied CTL activity of four patients, three were HLA A24-positive and one did not have HLA A24 but had B27 supertype. After an incubation of mononuclear cells with or without peptide and IL-2, CD8-rich fraction was prepared by treatment with Magnetic Cell Sorting system (MACS) twice. CTL activity was calculated by 51Cr release from transfectant, C1RA*2402 as target cells. The peptide-binding assay was examined by flow cytometry. RESULTS: Two of three HLA A 24-positive patients demonstrated CTL activity against the Yo peptide, AYRARALEL. CTL activity was found to be 19.5% and 11.7% at the effector/target (E/T) ratio of 23:1 and 11:1, respectively. A patient who did not have HLA A24 but had A2 and B27 supertype possessed a CTL activity of 19.4% with 15:1 as E/T ratio. The peptide could bind to HLA A*2402 molecules but not to A*0201. CONCLUSIONS: We showed CTL activity in two of three Japanese patients with HLA A24 by using HLA A*2402 transfectant cells as the target. In addition, we identified the first Japanese patient who had B27 supertype, and suggested that the same peptide, AYRARALEL, could be recognized by CTL in this patient.
Autoantigens↗
Transplantation of adult rat hippocampus-derived neural stem cells into retina injured by transient ischemia.
Neural stem cells are capable of differentiating along multiple central nervous system cell-type lineages, and their use as graft material has provided new strategies for the treatment of neuronal damage. We transplanted adult rat hippocampus-derived neural stem cells into eyes of adult rats that underwent ischemia-reperfusion injury. As control, the cells were also injected into normal rats eyes without ischemic insult. The rats were sacrificed at 1, 2, 4, and 8 weeks, and the eyes were examined histochemically. In eyes with the insult, the transplanted cells were well integrated into the host retinas and expressed Map2ab. In the control, none of the cells migrated into the retina. These results suggest that neural stem cells may be used as donor cells for transplantation to repair ischemic-injured retina.
Animals↗
Synthesis of hydrogels with extremely low surface friction.
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Biocompatible Materials↗
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.
Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.
Amino Acid Sequence↗
Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells.
Melanoma and renal cell carcinoma (RCC) are considered to be the most immunogenic tumors in humans. To generate conditions to induce primary T-cell responses against RCC and to allow further expansion of tumor-specific cytotoxic T lymphocytes (CTL) for adoptive transfer, peripheral blood mononuclear cells from RCC patients were stimulated with primary autologous tumor cells or monocyte-derived dendritic cells (DC) loaded with either tumor lysate (TU-LY) or apoptotic tumor cells (TU-AP). Whereas repetitive stimulation (4x) with tumor cells alone induced a predominant population of CD3(-) natural killer cells, 4 weeks of stimulation with tumor-loaded DC favored induction and expansion of CD4+ T cells (>80%). However, 2 weekly stimulation cycles with tumor-loaded DC followed by restimulation with autologous irradiated tumor cells alone were optimal for induction of tumor-specific CTL responses in vitro. Using these culture conditions a marked increase of CD4+ T cells was observed during the first 2 weeks of stimulation with tumor-loaded DC. Subsequent restimulation with autologous tumor cells alone gave rise to 500-fold expansion of CD8+ T cells. These CD8+ T cells were shown to exhibit strong major histocompatibility complex class I-restricted cytotoxic activity against the autologous tumor. Comparison of TU-LY and TU-AP as a source of tumor antigen for loading DC did not show any difference in stimulating tumor-specific CTL. Length pattern analysis of the complementary determining region 3 (CDR3) of the T-cell receptor Vbeta chain revealed expansion of oligoclonal CTL populations with outgrowth of 1 or 2 clones after prolonged stimulation with autologous tumor cells. Our study demonstrated an efficient method for generating tumor-specific CTL in vitro that may be used to identify tumor cell antigens or that can be expanded for adoptive T-cell transfer in tumor immunotherapy.
ATP-Binding Cassette Transporters↗
Age-related changes in manganese superoxide dismutase activity in the cerebral cortex of senescence-accelerated prone and resistant mouse.
In this paper, we showed that the oxidative stress in brain of senescence-accelerated prone mouse 8 (SAMP8) at earlier stages was increased compared with that of senescence-accelerated resistant mouse 1 (SAMR1) irrespective of the breeding conditions. Furthermore, we found that manganese superoxide dismutase (Mn-SOD) activity in the cerebral cortex of 10-week-old SAMP8 was decreased by about 50% compared with that in age-matched SAMR1. These results indicate that the decrease of Mn-SOD activity may be involved in the increased oxidative stress in the brain of SAMP8 at younger stages. However, there was no difference in the expression of this protein between the two strains at 10 weeks of age, suggesting that Mn-SOD protein in SAMP8 was post-translationally modified to reduce its enzymatic activity.
Aging↗