Expression and function of a recombinant endothelial nitric oxide synthase gene in porcine coronary arteries

PURPOSE: To evaluate the influence of prognostic factors in postoperative radiotherapy of NSCLC with special emphasis on the time interval between surgery and start of radiotherapy. METHODS AND MATERIALS: Between January 1976 and December 1993, 340 cases were treated and retrospectively analyzed meeting the following criteria: complete follow-up; complete staging information including pathological confirmation of resection status; maximum interval between surgery (SX) and radiotherapy (RT) of 12 weeks (median 36 days, range 18 to 84 days); minimum dose of 50 Gy (R0), and maximum dose of 70 Gy (R2). Two hundred thirty patients (68%) had N2 disease; 228 patients were completely resected (R0). One hundred six (31%) had adenocarcinoma, 172 (51%) squamous cell carcinoma. RESULTS: In univariate analysis, Karnofsky performance status (90+ >60-80%; p = 0.019 log rank), resection status stratified for nodal disease (R+ 相似文献   

Bleomycin-induced DNA damage and repair in wild-type and thymidine kinase-deficient Friend mouse erythroleukaemia cells

In this paper the DNA damage and repair induced by the radiomimetic agent bleomycin are compared in murine Friend erythroleukaemia wild-type 707 cells and a thymidine kinase-deficient sub-clone BUF. Comparisons are made using results obtained from the alkaline comet assay and unscheduled DNA synthesis experiments. Further analysis to determine the fidelity of bleomycin-induced repair as indicated by mutagenesis to hypoxanthine-phosphoribosyltransferase deficiency was also conducted. Similar sensitivities to bleomycin treatments were observed in the two cell types with the comet assay, while similar levels of dose-dependent excision repair following bleomycin treatments were also detected in unscheduled DNA synthesis experiments. Comet assay and unscheduled DNA synthesis experimental results are in agreement. Survival and induced hypoxanthine-phosphoribosyltransferase mutant frequencies were observed to be unaffected by a thymidine kinase-deficiency in Friend erythroleukaemia cells. The results of this investigation suggest no overall difference in the repair capacities or the repair fidelity of Friend 707 relative to BUF cells following bleomycin treatments.     

Clinical observation of the temporal association between crack cocaine and duodenal ulcer perforation

HYPOTHESIS: To determine if a cause-effect relationship exists between crack cocaine use and duodenal ulcer perforation (DUP). PATIENTS AND METHODS: A retrospective study was conducted of all patients undergoing emergency surgical management for peptic ulcer disease over a 6-year period at a large inner-city municipal teaching hospital. The hospital records of 78 consecutive patients presenting with complications of peptic ulcer disease between April 1990 and April 1996 were reviewed. Group A (n = 24) consisted of patients with confirmation of crack cocaine usage within 8 hours of clinical presentation; group B (n = 54) consisted of patients with no antecedent history of crack cocaine use. Demographic data, timing of drug use, clinical presentation, laboratory and radiographic findings, toxicology screening, operative findings, and postoperative course were compared between the two groups. RESULTS: Both groups revealed a similar gender distribution, tobacco use, prior peptic ulcer symptoms, and laboratory findings. Group A patients were younger (t test, P = 0.01) and more likely to present with perforation, whereas patients in group B presented with a combination of symptoms (chi square, P = 0.03). Duodenal ulcer perforation was present in 75% of patients in group A compared with 46% of patients in group B (chi square, P = 0.04). Group B patients had a significantly longer hospital stay compared with those in group A (t test, P = 0.01). Both crack cocaine and alcohol are independent predictors of duodenal ulcer perforation. CONCLUSIONS: Patients with recent use of crack cocaine and/or alcohol are more likely to present with duodenal perforations. Although a temporal association between crack cocaine use and duodenal ulcer perforation was demonstrated, this study does not confirm a cause-effect relationship. A prospective cohort study is needed to clarify the pathogenesis of this potential cause-effect relationship.     

Cell‐Tethered Ligands Modulate Bone Remodeling by Osteoblasts and Osteoclasts

The goals of the present study are to establish an in vitro co‐culture model of osteoblast and osteoclast function and to quantify the resulting bone remodeling. The bone is tissue engineered using well‐defined silk protein biomaterials in 2D and 3D formats in combination with human cells. Parathyroid hormone (PTH) and glucose‐dependent insulinotropic peptide (GIP) are selected because of their roles in bone remodeling for expression in tethered format on human mesenchymal stem cells (hMSCs). The cell‐modified biomaterial surfaces are reconstructed from scanning electron microscopy images into 3D models for quantitative measurement of surface characteristics. Increased calcium deposition and surface roughness are found in 3D surface models of silk protein films remodeled by co‐cultures containing tethered PTH, and decreased surface roughness is found for the films remodeled by tethered GIP co‐cultures. Increased surface roughness is not found in monocultures of hMSCs expressing tethered PTH, suggesting that osteoclast‐osteoblast interactions in the presence of PTH signaling are responsible for the increased mineralization. These data point towards the design of in vitro bone models in which osteoblast‐osteoclast interactions are mimicked for a better understanding of bone remodeling.     

Sexually transmitted disease acquisition among women infected with human immunodeficiency virus type 1

Recent evidence suggests that sexually transmitted diseases (STDs) enhance the transmission of human immunodeficiency virus (HIV) type 1. In 143 HIV-infected women enrolled in a university-based longitudinal HIV clinic over 16 months (mean), the STD point prevalence was examined at enrollment and the cumulative prevalence was calculated at follow-up. At enrollment, 35 women (25%) had > or = 1 STD. These included trichomoniasis in 16 women (11%); syphilis, 9 (6%); genital herpes, 8 (6%); gonorrhea, 5 (4%); chlamydia, 5 (4%); genital warts, 2 (1%); and pelvic inflammatory disease (PID), 1 (1%). STDs were found in 55 (42%) of the 125 patients who returned for at least one follow-up visit: trichomoniasis in 23 (18%); genital herpes, 20 (12%); gonorrhea, 9 (7%); syphilis, 7 (6%); genital warts, 7 (6%); chlamydia, 5 (4%); and PID, 4 (3%). Despite counseling at both enrollment and follow-up, these women had a very high cumulative prevalence of STDs, indicating persistent high-risk sexual behavior.     

Alterations in the expression of P2X1 receptors in failing and nondiseased human atria

This is the first report of the analysis of the ATP-specific P2X1 receptor subunit in human hearts. We have examined homogenate samples of human left atria for the presence of P2X1 receptors using Western blots. Anti-P2X1 immunoreactivity was detected in populations of nondiseased atria as well as in atria from explanted hearts from patients with terminally failing heart conditions such as dilated cardiomyopathy. At least three groups of P2X1 immunoreactive proteins were detected in the Western blots with approximate molecular mass values of 50, 70, and 160 kDa. We report changes in expression of their 50 and 70 kDa components. These changes may be related to the type of deficit in these hearts since the changes have been observed in hearts with decreased ejection fractions characteristic of dilated cardiomyopathy.     

Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study

PURPOSE: We evaluated the erectogenic properties of a new cyclic alpha-melanocyte-stimulating hormone analogue, Melanotan-II, to treat men with psychogenic erectile dysfunction. MATERIALS AND METHODS: Ten men with erectile dysfunction of no known organic cause were entered in a double-blind, placebo controlled crossover study in which the erectogenic properties of Melanotan-II and a vehicle placebo were compared using real-time RigiScan monitoring. The presence, duration and rigidity of erections were recorded during a 6-hour period. RESULTS: In 8 of 10 men treated with Melanotan-II clinically apparent erections developed. Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo (p=0.0045). Transient side effects of nausea, stretching and yawning, and decreased appetite were reported more frequently after injections of Melanotan-II than placebo but none required treatment. CONCLUSIONS: Melanotan-II is a potent initiator of erections in men with psychogenic erectile dysfunction and has manageable side effects at a dose of 0.025 mg./kg.     

Selective inhibition of [D-Ala2, Glu4]deltorphin antinociception by supraspinal, but not spinal, administration of an antisense oligodeoxynucleotide to an opioid delta receptor

Evidence in vivo has suggested the existence of subtypes of the delta opioid receptor (DOR), which have been termed delta 1 and delta 2. These proposed DOR subtypes are thought to be activated by [D-Pen2, D-Pen5]enkephalin (DPDPE, delta 1) and [D-Ala2, Glu4]deltorphin (delta 2). Recent work in which an antisense oligodeoxynucleotide (oligo) to a cloned DOR was administered by the intrathecal (i.th.) route has demonstrated a reduction in the antinociceptive actions of both i.th. DPDPE and [D-Ala2, Glu4]deltorphin, but not of [D-Ala2, NMPhe4, Gly-ol]enkephalin (DAMGO, mu agonist) in mice. The present investigation has extended these observations by administering the same DOR antisense oligo sequence by the intracerebroventricular (i.c.v.) route and evaluating the antinociceptive actions of i.c.v. agonists selective for delta, mu and kappa receptors. I.th. treatment with DOR antisense oligo, but not mismatch oligo, significantly inhibited the antinociceptive actions of both i.th. DPDPE and [D-Ala2, Glu4]deltorphin but not of i.th. DAMGO or U69,593 (kappa agonist), confirming previous data. In contrast, i.c.v. DOR antisense oligo, but not mismatch oligo, selectively inhibited the antinociceptive response to i.c.v. [D-Ala2, Glu4]deltorphin without altering the antinociceptive actions of i.c.v. DPDPE, DAMGO or U69,593. The data suggest that the cloned DOR corresponds to that pharmacologically classified as delta 2 and further, suggest that this delta receptor subtype may play a major role in eliciting spinal delta-mediated antinociception.