Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated -7 (mda-7)/interleukin-24 (IL-24) gene

We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (mda-7) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (P=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.     

Impact of Occluded Culprit Arteries on Long‐Term Clinical Outcome in Patients with Non‐ST‐Elevation Myocardial Infarction: 48‐Month Follow‐Up Results in the COREA‐AMI Registry

Background

The prognostic impact of occluded culprit arteries in non‐ST‐elevation myocardial infarction (NSTEMI) patients beyond 12 months has not been investigated.

Objectives

The impact of occluded culprit arteries on a composite of cardiac death (CD), recurrent nonfatal MI (RMI), and target vessel revascularization (TVR) in patients who presented with NSTEMI was investigated during a 48‐month follow‐up using propensity‐score (PS) matching.

Methods

A total of 2,878 NSTEMI patients in the COREA‐AMI (COnvergent REgistry of cAtholic and chonnAm university for Acute MI) Registry were classified according to the angiographic flow of culprit arteries (occlusion [OC], n = 1,070; nonocclusion, n = 1,808). After PS matching, the incidence of the primary end‐point, a composite of CD, RMI, and TVR was compared.

Results

The median follow‐up duration was 47.3 months (IQR 32.7–66.2). In the PS‐matched population, the 48‐month cumulative rates of the primary end‐point (27.5% vs. 17.9%, P < 0.001) and each event were higher in the OC group (CD: 9.0% vs. 5.4%, RMI: 16.3% vs. 9.4%, TVR: 10.5% vs. 5.6%, respectively, P < 0.05). In multivariate Cox regression analysis, occluded culprit arteries showed the significant statistical impact on the primary end‐point (HR 1.689 [1.385–2.059], P < 0.001) and each event (CD: 1.736 [1.218–2.475], RMI: 1.918 [1.468–2.505], TVR: 2.042 [1.453–2.869], respectively, P < 0.05). Furthermore, in the 12‐month landmark analysis, occluded culprit arteries were still associated with higher risk of primary end‐point beyond 12 months (P < 0.001).

Conclusions

Occluded culprit arteries were independently associated with the higher risk of CD, RMI, and TVR in NSTEMI patients during the 48‐month follow‐up. (J Interven Cardiol 2014;27:12–20)

     

Tensile Bond Strengths of Fourth- and Fifth-Generation Dentin Adhesives with Packable Resin Composites

Purpose: Placement of packable composites would be simplified if a single-bottle dentin bonding agent, rather than the more complex, multiple-bottle dentin bonding agents, involving multiple steps, could be used successfully with adequate bond strength. This study was designed to compare the tensile bond strengths to extracted human dentin of four single-bottle (fifth-generation) and four multiple-bottle (fourth-generation) dentin bonding agents with four packable composites.
Materials and Methods: Packable composites (P60, 3M Dental Products Division; ALERT, Jeneric-Pentron; Pyramid Dentin, Bisco; and Clearfil AP-X, Kuraray America) were tested for in vitro tensile bond strength to human dentin with their single-bottle and their multiple-bottle dentin bonding agents. Bond strengths were measured using a truncated cone tensile test, with a bonding diameter of 3 mm, after storage of specimens in water at 37°C and 100% relative humidity for 24 hours, and using a testing machine at a crosshead speed of 0.5 mm per minute.
Results : Means and standard deviations (n = 10) of tensile bond strengths (MPa) for the single-bottle system were P60, 21.3 MPa (6.7); ALERT, 26.6 MPa (4.2); Pyramid Dentin, 14.8 MPa (4.4); and Clearfil AP-X, 18.6 MPa ( 3.7 ). For the multiple-bottle system they were P60, 20.0 MPa (8.6); ALERT, 20.6 MPa (6.2); Pyramid Dentin, 16.0 MPa (3.4); and Clearfil AP-X, 17.8 MPa (6.0). Two-way analysis of variance showed significant differences among composites but no significant differences between single-bottle and multiple-bottle bonding agents. The Tukey-Kramer interval ( p < .05) for comparisons of bond strengths among composites was 4.8 MPa.
Conclusions: For single-bottle agents, bond strengths were ranked as ALFLRT > P60, P60 = Clearfil, P60 > Pyramid, and Clearfil = Pyramid. For multiple-bottle agents, there were no significant differences in bond strengths among the composites.     

Long‐Term Clinical Outcomes of the One‐Stent Technique versus the Two‐Stent Technique for Non‐Left Main True Coronary Bifurcation Disease in the Era of Drug‐Eluting Stents

Background

Few studies have compared the long‐term major adverse cardiac events (MACEs) between the one‐stent technique (stenting only the main branch) and the two‐stent technique (stenting of both the main and side branches) for the treatment of true coronary bifurcation lesions in the drug‐eluting stent era. Therefore, we investigated this issue using the large nationwide coronary bifurcation registry.

Methods

The 1,147 patients with non‐left main coronary true bifurcation lesions underwent percutaneous coronary intervention in the Korea Coronary Bifurcation Stent (COBIS) registry. All patients were stratified based on the stent placement technique: one stent (n = 898) versus two stents (n = 249). MACE, including death, nonfatal myocardial infarction (MI), and repeat vessel and lesion revascularization (TVR and TLR), were evaluated.

Results

The median follow‐up duration was 20 months. The MACEs did not differ between the 2 groups. Findings from the one‐stent group were similar to those of the two‐stent group in composite of death, MI, or TVR, based on analysis by crude, multivariate Cox hazard regression model, inverse‐probability‐of‐treatment weighting (hazard ratio [HR] 0.911, 95% confidence interval (CI) 0.614–1.351; HR 0.685 95% CI 0.381–1.232; HR 1.235, 95% CI 0.331–4.605, respectively). In further analysis with propensity score matching, the overall findings were consistent.

Conclusions

The findings of the present study indicate that the one‐stent technique was not inferior to the two‐stent technique for the treatment of non‐left main true coronary bifurcation lesions in terms of long‐term MACEs. (J Interven Cardiol 2013;26:245–253)

     

SYSTEMIC LUPUS ERYTHEMATOSUS IN 61 ORIENTAL MALES. A STUDY OF CLINICAL AND LABORATORY MANIFESTATIONS

The clinical and laboratory features of 61 oriental male lupuspatients were compared to those of 86 oriental female patientsto determine whether gender differences occur. Arthritis wassignificantly less common in the males. Neuropsychiatric disorderswere less frequent but the difference did not reach statisticalsignificance. Renal disease was the commonest clinical manifestationand diffuse proliferative glomerulonephritis the dominant histologicalfinding on renal biopsy in the males. The prevalences of leucopeniaandantibodies to extractable nuclear antigens in particular anti-Ro(SSA) and anti-La(SSB), were lower in men. Arthritis and serositiswere less common in our oriental males in contrast to the Caucasianpatients. These findings provide further evidence of differencesbetween the genders in SLE and suggest racial factors may affectclinical presentation. KEY WORDS: Male lupus, Arthritis, Leucopenia, Anti-Ro, Anti-La, Serositis     

Rate of Hanger Reflex Occurrence: Unexpected Head Rotation on Fronto-temporal Head Compression

When the head is encircled with a wire clothes hanger and the unilateral fronto-temporal region is compressed, the head rotates unexpectedly. As the mechanism is unclear, however, we have temporarily named this phenomenon as the “hanger reflex.” We previously reported a case wherein this phenomenon was applied to treat cervical dystonia. Because little is known about this phenomenon, we determined how often this phenomenon is observed in healthy subjects. Study participants were 120 healthy Japanese adults (60 men and 60 women) aged 19–65 years. A wire clothes hanger was applied to each subject’s head. The longer side of the hanger was attached over the volunteer’s fronto-temporal regions on both sides of the head in succession (i.e., two applications per volunteer). We evaluated whether the subjects felt the sensation of head rotation by using a questionnaire. The sensation of head rotation was observed in 95.8% of subjects. There were five non-responders (4.2%). In 85.4% of the trials, head rotation was observed in the direction that coincided with the side compressed by the hanger. There were no differences in responses between genders. The incident rate of the hanger reflex was remarkably high and most likely represents a prevalent phenomenon in humans. The mechanism underlying the reflex remains unknown. Further research should be performed to elucidate the underlying causes of the hanger reflex, which represents a potential treatment for cervical dystonia.     

Human chorionic gonadotropin prevents Sjögren's syndrome-like exocrinopathy in mice

OBJECTIVE: Results of recent studies suggest that human chorionic gonadotropin (HCG), a placental glycoprotein hormone required for the maintenance of pregnancy, may have immunomodulatory properties. Primary Sj?gren's syndrome (SS), a chronic autoimmune disorder of unknown etiology, affects multiple exocrine glands including the salivary and lacrimal glands. The purpose of the present study was to determine whether HCG could prevent the development of salivary gland exocrinopathy in NOD mice, an experimental model of Sj?gren's-like syndrome. METHODS: Female NOD mice were treated with HCG from 6 weeks of age to 12 weeks of age. At 14 weeks, tissue samples were evaluated for inflammatory lesions and cytokine messenger RNA by real-time polymerase chain reaction. At 18 weeks, the salivary flow rate was measured. RESULTS: Treatment with HCG resulted in a significant decrease in lymphocyte infiltration and parenchymal cell damage in the submandibular salivary glands. Messenger RNA levels of interferon-gamma, tumor necrosis factor alpha, interleukin-1beta, and interleukin-10, as well as inducible nitric oxide synthase and matrix metalloproteinase 9, were significantly decreased. Function studies revealed a marked increase in the salivary flow rate in HCG-treated mice compared with that in phosphate buffered saline-treated mice. CONCLUSION: In NOD mice, HCG acts as an immune modulator and prevents the development of salivary gland exocrinopathy. These findings suggest that HCG, a naturally occurring reproductive hormone, may be useful in the treatment of Sj?gren's syndrome and other human autoimmune diseases.     

Training of nurses in ear examination and hearing screening in the school setting

The objectives of this study were to determine the agreement between the ear examination findings of the otorhinolaryngologist (trainer) and the elementary school nurse (trainee) after training with the use of a penlight and to determine the mean sound pressure level (SPL) produced by school nurses as a standard parameter for hearing screening using a 512 tuning fork after training on tuning fork testing by the otorhinolaryngologist. Training workshops in ear examination using a penlight and hearing screening using a 512 tuning fork were conducted for school nurses. Data for assessment of ear examination skills and production of SPL were collected by questionnaire and observation of performance. Kappa statistics were used to assess agreement between trainees' and trainer's responses. Mean and standard deviation were determined for the assessment of the SPL produced. Results showed an excellent agreement between the school nurses' and otorhinolaryngologist's observations on ear examination. These included observations of the ear canal, visualization of the tympanic membrane and identification of unusual findings such as wax and discharge. The majority of nurses responded positively in terms of the ease and confidence in performance of the procedure. Regarding tuning fork testing, the nurses were able to produce significant SPL. The mean SPL produced by the nurses using a 512 tuning fork was 56.316 dB.     

Review: Relationship of type 2 diabetes to human brain pathology

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high‐morbidity and high‐mortality. Numerous clinical studies have consistently shown that T2D confers a two‐fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT), are also posited mechanisms. The clinicopathological studies to date demonstrate T2D to be consistently associated with infarcts, particularly subcortical lacunar infarcts, but not ADNC, suggesting the association of T2D with dementia may largely be mediated through CVD. Furthermore, growing interest exists in insulin resistance (IR), particularly IR within the brain itself, which may be an associated but distinct phenomenon from T2D, and possibly itself associated with ADNC. Other mechanisms largely related to protein processing and efflux in the central nervous system with altered function in T2D may also be involved. Such mechanisms include islet amyloid polypeptide (or amylin) deposition, co‐localized with beta‐amyloid and found in more abundance in the AD temporal cortex, blood‐brain barrier breakdown and dysfunction, potentially related to pericyte degeneration, and disturbance of brain lymphatics, both in the glial lymphatic system and the newly discovered discrete central nervous system lymph vessels. Medical research is ongoing to further disentangle the relationship of T2D to dementia in the ageing human brain.