Cellular sources of transforming growth factor-alpha in human oral cancer

Aberrant expression of TGF-alpha is associated with human malignant oral epithelium. Experiments were initiated to determine the cellular sources of transforming growth factor-alpha (TGF-alpha) in human oral cancer. Ten freshly resected human oral cancers and four specimens of normal human oral epithelium were studied by in situ hybridization and immunohistochemistry. Tissues were probed with 35S-labeled sense and antisense riboprobes to (i) human TGF-alpha (hTGF-alpha), (ii) human epidermal growth factor receptor (EGFR) to determine the distribution of TGF-alpha responsive cells, and (iii) histone H3 to examine TGF-alpha and/or EGFR's possible contribution to altered proliferation in transformed epithelium. Results of our experiments showed that TGF-alpha mRNA could be detected in normal and transformed human oral epithelium. More surprising, we have identified the major source of TGF-alpha mRNA to be the infiltrating eosinophils. A monoclonal antibody to the mature human TGF-alpha peptide stained similar areas in normal and malignant specimens. Eosinophils associated with tumors exhibited positive cytoplasmic immunostaining for TGF-alpha protein. Labeling of EGFR mRNA in human oral epithelium demonstrated uniform labeling of basal layers in normal, hyperplastic, and mildly dysplastic epithelium. In severely dysplastic epithelium and carcinomas (particularly moderate to poorly differentiated types), cellular levels of EGFR mRNA were significantly higher. The profile of altered cellular levels of EGFR mRNA correlated well with the profile of altered proliferation as indicated by H3 mRNA labeling. We hypothesize that the overproduction of EGFR mRNA in tumor epithelium--together with the localized delivery of high amounts of TGF-alpha by eosinophils at tumor-developing sites--is responsible for the increased proliferation of the tumor epithelium.     

Enhanced natural killer cell activity in patients with cervical carcinoma by postoperative PS-K immunotherapy

The cell-mediated immunity in 19 patients with stage I and II cervical carcinoma was evaluated before and after postoperative PS-K immunotherapy. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leullb, Leu15, and Leu19) and the OKT series (OKT3, and OKT4). A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. Serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R), and tumor necrosis factor (TNF) were also determined before and after postoperative PS-K immunotherapy. The results showed that the number of cells carrying the marker of a non-major histocompatibility complex (MHC), restricted cytotoxic lymphocytes in the peripheral blood and NK activity at three different effector/target ratios increased significantly after postoperative PS-K immunotherapy. It is therefore concluded that postoperative PS-K immunotherapy enhanced the NK activity in patients with cervical carcinoma, in which NK activity tended to be lower. Further clinical investigation to assess the effectiveness of PS-K immunotherapy in improving the overall survival is in progress.     

Preliminary effects of hyaluronic acid on early rehabilitation of patients with isolated anterior cruciate ligament reconstruction.

OBJECTIVE: To investigate the effects of Hyaluronic acid (HA) on early rehabilitation of patients with isolated anterior cruciate ligament (ACL) reconstruction. DESIGN: Randomized, controlled clinical trial. SETTING: A total 120 patients with isolated ACL injury who had received patellar tendon autograft reconstruction were randomly assigned to four groups (groups I-IV), with 30 subjects in each group. INTERVENTIONS: All patients received 16 weeks of a regular rehabilitation program and an intra-articular injection of HA or saline weekly for 3 weeks. Additionally, patients in group I received the HA commencing at 4 weeks after surgery, patients in group II at 8 weeks, and patients in group III at 12 weeks. Patients in group IV did not receive HA but did receive the same volume of normal saline as control subjects at 4 weeks after surgery. The rehabilitation program started at the same time after surgery for all groups. MAIN OUTCOME MEASUREMENTS: Outcomes were measured at 4, 8, 12, and 16 weeks after reconstruction, and at follow-up 1 year later. These included the changes in Lysholm knee scoring scale, knee range of motion, ambulation speed (AS), and muscle peak torque (MPT) of knee flexion and extension. RESULTS: There were improvements in groups I-III shortly after receiving the HA, but not in the saline group (group IV). Patients in groups II and III showed more improvement in AS and MPT after rehabilitation program and at follow-up. Besides, the best results 1 year later occurred in the group receiving HA at 8 weeks after surgery (group II). CONCLUSION: HA therapy results in more functional and MPT improvement in ACL rehabilitation, and the intervention at 8 weeks after surgery results in the best outcome.     

Production of Transforming Growth Factor Alpha by Hamster Eosinophils

Previously it was demonstrated that malignant transformation of the Syrian hamster cheek pouch mucosa is associated with the expression of TGF-alpha. Therefore in situ hybridization and immunohistochemistry was used to investigate the cellular sources of TGF-alpha production in this model system. Surprisingly one cell type in the inflammatory infiltrate present in the connective tissue adjacent to the transformed epithelium represented a major source of TGF-alpha mRNA. Detailed analysis of these cells revealed that they were eosinophils. In addition to TGF-alpha mRNA, about 40% of the eosinophils associated with the oral tumors exhibited TGF-alpha product reactive with a monoclonal antibody against the C terminus of the mature TGF-alpha peptide. Normal hamster bone marrow eosinophils also exhibited TGF-alpha mRNA and product by in situ hybridization and immunohistochemistry. These results suggest that the eosinophil represents a biologically significant source of TGF-alpha.     

Initial experience with a new femoral artery closure device following percutaneous coronary intervention with glycoprotein IIb/IIIa inhibition.

The aim of the study was to determine the safety and efficacy of a novel femoral artery closure device (StarClose, Abbott Vascular Devices, Redwood City, CA) following percutaneous coronary intervention employing aspirin, heparin, and glycoprotein (GP) IIb/IIIa inhibition. A prospective nonrandomized single-center pilot study of the StarClose device included a subset of patients undergoing percutaneous coronary intervention utilizing GP IIb/IIIa inhibitors. Those that fulfilled the inclusion criteria (age < 80, no periprocedural haematoma, puncture above the superficial femoral and profunda femoralis artery bifurcation, no significant femoral artery disease) underwent closure of the femoral artery puncture site with a StarClose device immediately on completion of the procedure. Time to hemostasis (TTH), bleeding, mobilization, and short-term clinical follow-up data were collected, and an ultrasound scan of the femoral artery was performed 2 weeks later. Twenty-five patients were recruited, of whom 23 underwent percutaneous coronary intervention (PCI). Their mean age was 58 +/- 12 years, 84% were male, and 63% had unstable angina. All were on aspirin 100-150 mg daily and all PCI patients received i.v. heparin 4-10,000 units at commencement of the procedure and clopidogrel 600 mg on completion. Two patients were on a tirofiban infusion and 23 received a double bolus of eptifibatide, each 0.18 mg/kg, separated by 10 min. The procedural success was 100% and device success 23/25 (92%), with 1 failure due to technical error. The median device delivery time was 36 sec (range, 11-178) and median TTH 37 sec (range, 10-509 sec). There were no major adverse events. In 10 patients, a moderate amount of tract ooze required a short period of adjunctive manual compression. Follow-up ultrasound femoral artery scans revealed no compromise of the vessel lumen. Femoral artery closure with the device following coronary angiography and intervention using glycoprotein IIb/IIIa receptor inhibitors is safe and effective. A randomized trial of a larger number of patients is warranted.     

Postpartum Taiwanese women: their postpartum depression, social support and health-promoting lifestyle profiles

Background. To reach the Millennium Development Goals, maternal health‐promoting behaviours need to be encouraged after childbirth; little is known about the health‐promoting behaviour among first‐time mothers during their postpartum period. Aim. To examine levels of engagement in health‐promoting behaviours and related factors among postpartum women in Taiwan. Methods. This cross‐sectional study was conducted through a convenience sample of 122 qualified women. Participants self‐completed a questionnaire and mailed it back using a stamped, self‐addressed envelope from July to September 2003. Instruments of this study included a demographic questionnaire as well as three Likert‐type scales: the Health Promotion Lifestyle Profile scale, the Edinburgh Postnatal Depression scale and a self‐developed social support scale. Results. The average overall Health Promotion Lifestyle Profile score was low (mean, 2·83 SD 1·35), with exercise rated lowest among the six subscales. Postpartum women perceived that they had high levels of social support from their mothers‐in‐law, mothers and husbands. An astonishing 42·6% of women experienced postnatal depression. Based on results of multiple regressions, 25% of the variance in health‐promoting lifestyle practices was explained by postpartum depression and social support. Social support was found to predict all subscales significantly except exercise. Postpartum depression can significantly predict self‐actualization, interpersonal relationships, nutrition and stress management. All modifying factors were excluded from the regression model. Conclusions. This study validates the theoretical relationships among concepts in the Health Promotion Model. Nursing interventions are recommended which are tailored to enhance women's social support and decrease their depression to promote their pursuit of healthy lifestyles. Relevance to clinical practice. This study highlights the implications of social support to nursing practice, especially in Chinese culture which has a strict ritual during a women's postpartum period. Findings of this study provide information and data for service planning and community care to support postpartum care in the communities.     

The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial

BACKGROUND: Complementary and alternative medicine use in adults with type 2 diabetes is popular. Although most of the herbs and supplements appear to be safe, there is still insufficient evidence that demonstrates their definitive beneficial effects. This study was done to determine whether the supplement of Agaricus blazei Murill extract improves insulin resistance in type 2 diabetes. MATERIALS AND METHODS: This study was a clinical randomized, double-blind, placebo-controlled trial. Of a population of 536 registered diabetes patients with 72 subjects (1) aged between 20 and 75 years, (2) being Chinese, (3) having type 2 diabetes for more than 1 year, and (4) having been taking gliclazide and metformin for more than 6 months were enrolled in this study. The enrolled patients were randomly assigned to either receiving supplement of Agaricus blazei Murill (ABM) extract or placebo (cellulose) 1500 mg daily for 12 weeks. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the major outcome measurement. RESULTS: At the end of the study, subjects who received supplement of ABM extract (n = 29) showed significantly lower HOMA-IR index (3.6[standard deviation, 2.5] versus 6.6[standard deviation, 7.4], p = 0.04) than the control group (n = 31). The plasma adiponectin concentration increased 20.0(standard deviation, 40.7)% in the ABM group after 12 weeks of treatment, but decreased 12.0(20.0)% among those taking the placebo (p < 0.001). CONCLUSIONS: Supplement of ABM extract improves insulin resistance among subjects with type 2 diabetes. The increase in adiponectin concentration after taking AMB extract for 12 weeks might be the mechanism that brings the beneficial effect. Studies with longer periods of follow-up should be conducted in the future.     

D-501036, a novel selenophene-based triheterocycle derivative, exhibits potent in vitro and in vivo antitumoral activity which involves DNA damage and ataxia telangiectasia-mutated nuclear protein kinase activation

D-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole] is herein identified as a novel antineoplastic agent with a broad spectrum of antitumoral activity against several human cancer cells and an IC(50) value in the nanomolar range. The IC(50) values for D-501036 in the renal proximal tubule, normal bronchial epithelial, and fibroblast cells were >10 mumol/L. D-501036 exhibited no cross-resistance with vincristine- and paclitaxel-resistant cell lines, whereas a low level of resistance toward the etoposide-resistant KB variant was observed. Cell cycle analysis established that D-501036 treatment resulted in a dose-dependent accumulation in S phase with concomitant loss of both the G(0)-G(1) and G(2)-M phase in both Hep 3B and A-498 cells. Pulsed-field gel electrophoresis showed D-501036-induced, concentration-dependent DNA breaks in both Hep 3B and A-498 cells. These breaks did not involve interference with either topoisomerase-I and topoisomerase-II function or DNA binding. Rapid reactive oxygen species production and formation of Se-DNA adducts were evident following exposure of cells to D-501036, indicating that D-501036-mediated DNA breaks were attributable to the induction of reactive oxygen species and DNA adduct formation. Moreover, D-501036-induced DNA damage activated ataxia telangiectasia-mutated nuclear protein kinase, leading to hyperphosphorylation of Chk1, Chk2, and p53, decreased expression of CDC25A, and up-regulation of p21(WAF1) in both p53-proficient and p53-deficient cells. Collectively, the results indicate that D-501036-induced cell death was associated with DNA damage-mediated induction of ataxia telangiectasia-mutated activation, and p53-dependent and -independent apoptosis pathways. Notably, D-501036 shows potent activity against the growth of xenograft tumors of human renal carcinoma A-498 cells. Thus, D-501036 is a promising anticancer compound that has strong potential for the management of human cancers.     

The relationships between disability level, health-promoting lifestyle, and quality of life in outpatients with systemic lupus erythematosus

The purpose of this study was to explore the relationships between disability, health-promoting lifestyle and quality of life in SLE outpatients. Cross-sectional research design and purposive sampling were used in this study. One hundred and twenty-nine SLE outpatients from a medical center were sampled. Questionnaires, including the Visual Analogue Scale, Pittsburgh Sleep Quality Index, and The Hospital Anxiety and Depression Scale, were adopted in order to survey subject disabilities in terms of pain, fatigue, quality of sleep, anxiety, and depression. Health-promoting lifestyle was measured using the Health-Promoting Lifestyle Profile, while quality of life data were collected using Short-Form 36. Hierarchical regressions and a Sobel test were the major statistical procedures employed. Study results indicated that SLE patient self-reported pain and fatigue related to the SLE disease to be 27.7 +/- 26.2 and 37.4 +/- 26.6, respectively. Seventy-two percent of SLE patients were reported to be troubled by poor sleep quality, while 20%-32% suffered from severe anxiety and depression. The Health-Promoting Lifestyle Profile total score for SLE patients was 61.5 +/- 17.2. In terms of SLE patient quality of life (QOL), physical component summary (PCS) and mental component summary (MCS) scores were 45.3 +/- 9.1 and 43.8 +/- 9.7, respectively. Based on the hierarchical regressions and Sobel test, it was revealed that the health-promoting lifestyle has no significant effect on the physical component summary (p > .05). Fatigue was the mediator factor of health-promoting lifestyle to physical component summary of quality of life. Nevertheless, health-promoting lifestyle has a significant effect on the mental component summary (p <.05). Interestingly, the results showed facilitating health- promoting lifestyle in SLE patient could not enhance physical component summary of quality of life directly without an improvement in fatigue disability; however, facilitating health-promoting lifestyle had a direct and positive effect on the mental component summary of quality of life.