Upregulation of P-selectin and intercellular adhesion molecule-1 after retinal ischemia-reperfusion injury

PURPOSE: Vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules, after retinal ischemia. They mediate the transmigration process of leukocytes. For further understanding of the role of leukocytes after retinal ischemia-reperfusion injury, the responses of the leukocyte-endothelial cell adhesion molecules P-selectin and intercellular adhesion molecule (ICAM)-1 during retinal ischemia and reperfusion were examined. METHODS: Male pigmented rats were subjected to retinal ischemia by a 1-hour ligation of the optic nerve followed by reperfusion. Gene and protein expression of P-selectin and ICAM-1 were studied at 0.5, 1, 6, 12, and 24 hours after the onset of reperfusion with semiquantitative polymerase chain reaction and Western blot analysis. Immunohistochemical methods were used to detect specific lesions expressing ICAM-1. RESULTS: Significant upregulation of P-selectin and ICAM-1 mRNA (at 6, 12, and 24 hours of reperfusion) were observed, with the expression peaks of both P-selectin and ICAM-1 mRNA occurring at 12 hours after reperfusion. P-selectin protein gradually increased and reached a maximum 6 hours after reperfusion, whereas ICAM-1 protein increased until 24 hours after reperfusion. Immunostaining with ICAM-1 antibodies was positive in endothelial cells after ischemia-reperfusion injury. CONCLUSIONS: Retinal ischemia-reperfusion stimulates P-selectin and ICAM-1 expression. Endothelial ICAM-1 expression in retinal vessels was observed. Upregulation of P-selectin and ICAM-1, which contribute to leukocyte rolling and adhesion, were observed after retinal ischemia.     

Reduced nitric oxide synthase in the brainstem contributes to enhanced sympathetic drive in rats with heart failure

Recent studies have suggested that central nervous mechanisms are involved in the enhanced sympathetic drive observed in heart failure (HF). Nitric oxide (NO) in the brainstem has been shown to reduce sympathetic nerve activity. The aim of this study was to determine whether the expression of neuronal nitric oxide synthase (nNOS) in the brainstem is reduced in rats with HF. Heart failure was produced by myocardial infarction in Wistar-Kyoto rats (HF group). Hemodynamic and echocardiographic examinations were performed. Western blot analysis for nNOS in the nucleus tractus solitarii (NTS) and the rostral ventrolateral medulla (RVLM) in the brainstem were performed to determine the expression of the nNOS gene in the HF group or sham-operated (control) group. We also performed in situ hybridization for nNOS mRNA and distribution in the brainstem. The expression of nNOS protein in the NTS and the RVLM were reduced in the HF group compared to the control group. The expression of nNOS mRNA in the brainstem was also reduced in the HF group, particularly in the NTS, compared to the control group. Intracisternal injection of NG-monomethyl-L-arginine elicited a smaller pressor response in the HF group than in the control group. These results suggest that reduced nNOS expression in the NTS and the RVLM, and the resulting reduced NO production of these sites, contribute to the enhanced sympathetic drive in HF.     

Clinical implication of morning blood pressure surge in hypertension

Cardiovascular events occur most frequently in the morning. The morning surge in blood pressure may be associated with hypertensive target organ damage and subsequent cardiovascular risk in hypertensive patients. In our prospective study on elderly hypertensive patients, the morning blood pressure surge (defined as the increase from the lowest blood pressure during sleep to the average of the first 2 h after waking) was significantly associated with silent hypertensive cerebrovascular disease and subsequent stroke risk. This association was independent of age and 24-h ambulatory blood pressure levels. In addition, even after controlling for these factors and status of silent cerebrovascular disease, the contribution of the morning blood pressure surge remained significant, and a 10 mmHg increase in systolic morning blood pressure surge increase the stroke risk by 22%. A related factor is orthostatic hypertension, which might be associated with increased sympathetic activity, and which is significantly associated with an increase in morning blood pressure surge and ambulatory blood pressure variability. A possible implication is that, in addition to strict blood pressure control, antihypertensive medication that targets exaggerated morning blood pressure may achieve more effective prevention of cardiovascular events in hypertensive patients.     

The role of lipopolysaccharide in T-cell responses following DNA vaccination

Bacterial products, including lipopolysaccharide (LPS), are potential impurities in plasmid DNA vaccines. LPS has immunostimulatory properties even at exceedingly low concentrations through activation of Toll-like receptor 4 (TLR4). The potency of T-cell responses after vaccination was tested with DNA containing high LPS or depleted of LPS in TLR4-competent and TLR4-deficient mice. CD8(+) T-cell responses were readily induced in TLR4-deficient mice immunized with DNA depleted of LPS. LPS in DNA vaccines is not required for CD8(+) T-cell responses.     

Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital-based case-control study in Japan

We assessed the possible association of gastrointestinal cancers with cruciferous vegetables and mushrooms in a multicenter, hospital-based case-control study in an agricultural area of Japan. One hundred forty-nine cases and 287 controls for stomach cancer and 115 cases and 230 controls for colorectal cancer were matched by age, sex, and residential area. In stomach cancer, the protective effect of vegetables (consumption of total vegetable) was obscure, but it became clearer when we examined specific kinds of vegetables. Marginal associations were observed in the group of the highest consumption of Chinese cabbage (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.35-1.07), broccoli (OR = 0.60; 95% CI = 0.34-1.08), Hypsizigus marmoreus (Bunashimeji) (OR = 0.57; 95% CI = 0.31-1.04) and Pholita nameko (Nameko) (OR = 0.56; 95% CI = 0.30-1.06). In colorectal cancer, we observed decreased risks from the highest tertile of total vegetables (OR = 0.22; 95% CI = 0.08-0.66) and low-carotene-containing vegetables (OR = 0.28; 95% CI = 0.08-0.77), and inverse associations were observed in the group of the highest consumption of broccoli (OR = 0.18; 95% CI = 0.06-0.58). Although the sample size was limited, subgroup analyses showed that the associations differed with the histopathological subtype. These findings suggest that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer.     

New method of catheter-port system implantation in hepatic arterial infusion chemotherapy

BACKGROUND: This report describes a novel method of implantation of the catheter-port system in hepatic arterial infusion chemotherapy, which is the inferior epigastric arterial approach. METHODS: Using this method, the length of incision is about 3 cm in lower abdomen. The inferior epigastric artery is exposed above the inguinal ligament. The half of the artery is cut, and a vascular sheath is inserted into the external iliac artery along a guide wire. A catheter is inserted into the hepatic artery through the vascular sheath. Coil occlusion of nontarget artery is performed by the technique of interventional radiology. Then the vascular sheath is removed and the catheter is fixed to the inferior epigastric artery. A port is connected to the catheter and placed above the incision in the lower abdomen. CONCLUSIONS: Using this method, the hip joint can be moved freely and port-related complications are few, which contributes to a good quality of life of patients during the therapy. The inferior epigastric arterial approach may give a benefit to those who are treated with hepatic arterial infusion chemotherapy.     

Spine fusion using cell matrix composites enriched in bone marrow-derived cells

Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting.     

Hand assisted retroperitoneoscopic nephroureterectomy: comparison with the open procedure

PURPOSE: We report our initial experience with hand assisted retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma and compared our results to those of a contemporary series of open nephroureterectomy. MATERIALS AND METHODS: Clinical data on 34 consecutive patients who underwent hand assisted retroperitoneoscopic nephroureterectomy were reviewed and compared with those on 34 who underwent open nephroureterectomy. All specimens were extracted intact. RESULTS: Total operative time was similar in the 2 groups (233 versus 236 minutes). Estimated blood loss was significantly less in the hand assisted laparoscopy group (236 versus 427 ml.). During convalescence the frequency of parenteral analgesia postoperatively was significantly lower in the laparoscopy group than in the open surgery group. The former patients had a significantly shorter interval to oral intake and ambulation as well as a shorter hospital stay and convalescence compared with those who underwent open surgery. In each group the complication rate was 12% (4 of 34 cases). In the hand assisted laparoscopy group 1 conversion to an open procedure was due to bleeding. There was recurrence in 4 of the 34 patients (12%) in the laparoscopy group, including 2 with bladder recurrence and 2 with metastases, at an average followup of 13.1 months. CONCLUSIONS: Hand assisted retroperitoneoscopic nephroureterectomy is an effective and safe alternative to open nephroureterectomy for upper urinary tract transitional cell carcinoma.     

Analysis of 15 short tandem repeats reveals significant differences between the Arabian populations from Morocco and Syria

The short tandem repeat (STR) systems D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA were studied in Arabian population samples from Morocco and Syria. No significant deviation from Hardy-Weinberg equilibrium could be observed in either preparation. Comparing the Moroccan and Syrian populations using the program RxC, no similarity could be observed at all 15 loci. In the Moroccan and Syrian populations the matching probability is 1 in 1.4 x 10(17) and 1 in 2.6 x 10(17), respectively. Thus, the combination of these 15 STR loci is powerful tool for forensic identification in Arabian populations.     

Genetic susceptibility to thymic lymphomas and K-ras gene mutation in mice after exposure to X-rays and N-ethyl-N-nitrosourea

PURPOSE: Ras activation is one of the major mechanisms for the development of murine thymic lymphomas by radiation and chemical carcinogens. To gain insight into the relationship between genetic susceptibility and ras gene mutation, the frequency and spectrum of ras gene mutation was examined in thymic lymphomas from susceptible and resistant mice. MATERIALS AND METHODS: K- and N-ras mutations in thymic lymphomas that arose in X-ray-irradiated and N-ethyl-N-nitrosourea (ENU)-treated mice of susceptible C57BL/6, rather resistant C3H and their hybrid B6C3F1 were analysed by polymerase chain reaction-single-strand conformation polymorphism and subsequent DNA sequencing. RESULTS: C57BL/6 exhibited a higher incidence of thymic lymphomas after exposure to X-rays and ENU than C3H, with B6C3F1 being intermediate. K-ras gene mutations occurred frequently in the pathogenesis of ENU-induced thymic lymphomas in susceptible C57BL/6 as opposed to resistant C3H. The ras mutations were more frequent in ENU-induced thymic lymphomas than X-ray-induced thymic lymphomas, and with the latter, there was no clear evidence for strain differences, suggesting that the genetic susceptibility to X-rays was independent of ras activation. The mutations of K-ras in thymic lymphomas from C57BL/6 were predominantly GGT to GAT in codon 12, whereas this mutation type was never found in those from C3H. No strain difference was observed in the nucleotide sequence or expression levels of O(6)-alkylguanine alkyltransferase, indicating that this enzyme did not account for the genetic susceptibility to ras activation. CONCLUSIONS: The results indicate that there is a clear strain and carcinogen dependency of K-ras mutation and that the frequency of ras mutation might determine the genetic susceptibility to ENU-induced lymphomagenesis, whereas pathways independent of ras activation might determine the susceptibility to X-ray-induced lymphomagenesis.