Amniotic fluid protease activity, protease inhibitory activity, and fetal lung maturity

Amniotic fluid acid protease and acid protease inhibitory activities were examined in normal pregnancies as a function of gestational age. The acid proteolytic activity of the amniotic fluid is almost constant during gestational weeks 16-29 (26 +/- 13 micrograms globin/ml/2 hrs, mean +/- SD, n = 64). The activity sharply increases after 29 weeks in a time-dependent fashion and reaches a value of 302 +/- 89 (mean +/- SD, n = 13) at 39-40 weeks gestation. Under standard conditions, the ability of amniotic fluid to inhibit bovine pepsin declined during gestation in a linear fashion from 44 +/- 13% (mean +/- SD, n = 36) at 16-18 weeks to 9 +/- 10% (mean +/- SD, n = 41) at 36-40 weeks. A correlation coefficient of r = 0.72 was found between pepsin inhibitory activity and gestational age. No consistent change was noted in the extent of inhibition of the endogenous acid protease throughout pregnancy. In 61 amniotic fluid samples, a correlation coefficient of r = 0.70 was found between acid protease activity and the lecithin/sphingomyelin (L/S) ratio. During the course of this study, five cases of respiratory distress syndrome (RDS) were diagnosed clinically. All five infants had a low protease activity (55 +/- 22 micrograms globin/ml/2 hr, mean +/- SD) as well as a low L/S ratio (0.68 +/- 0.20, mean +/- SD). In contrast, no case of RDS of the newborn was observed among 29 pregnancies with high protease activity and a high L/S ratio. The present observations may suggest a predictive value of amniotic fluid acid protease activity in assessment of fetal lung maturity.     

Multiple mechanisms govern the dynamics of depression at neocortical synapses of young rats

Synaptic transmission between pairs of excitatory neurones in layers V ( N = 38) or IV ( N = 6) of somatosensory cortex was examined in a parasagittal slice preparation obtained from young Wistar rats (14–18 days old). A combined experimental and theoretical approach reveals two characteristics of short-term synaptic depression. Firstly, as well as a release-dependent depression, there is a release-independent component that is evident in smaller postsynaptic responses even following failure to release transmitter. Secondly, recovery from depression is activity dependent and is faster at higher input frequencies. Frequency-dependent recovery is a Ca²⁺-dependent process and does not reflect an underlying augmentation. Frequency-dependent recovery and release-independent depression are correlated, such that at those connections with a large amount of release-independent depression, recovery from depression is faster. In addition, both are more pronounced in experiments performed at physiological temperatures. Simulations demonstrate that these homeostatic properties allow the transfer of rate information at all frequencies, essentially linearizing synaptic responses at high input frequencies.     

Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo.

PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine.     

A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.

PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor.     

Successful delivery following myocardial ischemia during the second trimester of pregnancy

Acute myocardial infarction during pregnancy is considered to be associated with approximately 50% mortality of both mother and fetus. However, there are not enough data regarding the role of acute myocardial ischemia. We present a 36-year-old, pregnant, white female who was admitted twice at 18 and 20 weeks of gestation with acute myocardial ischemia. Cardiac catheterization revealed 70–80% stenosis of the mid left anterior descending artery (LAD) with normal antegrade flow and very good retrograde filling of the LAD from distal collaterals of the right coronary artery. Therefore, due to angiographic suggestion of protected LAD territory, we recommended medical therapy and scheduled a vaginal delivery that was successfully completed without cardiovascular complications. A stress thallium test performed 6 months later was normal, supporting our clinical judgment. In conclusion, every case of a pregnant woman with coronary insufficiency should be treated according to individual coronary anatomy and blood supply to the territory of the diseased artery, and should not be based on the old data in the literature. The decision for revascularization prior to delivery versus medical therapy, or Caesarean section versus natural delivery, should be made by a team of a cardiologist and an obstetrician.     

Subclinical atherosclerosis in psoriatic arthritis: a case-control study

OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.     

Isolated foveal hypoplasia with secondary nystagmus and low vision is associated with a homozygous SLC38A8 mutation

Foveal hypoplasia, always accompanied by nystagmus, is found as part of the clinical spectrum of various eye disorders such as aniridia, albinism and achromatopsia. However, the molecular basis of isolated autosomal recessive foveal hypoplasia is yet unknown. Individuals of apparently unrelated non consanguineous Israeli families of Jewish Indian (Mumbai) ancestry presented with isolated foveal hypoplasia associated with congenital nystagmus and reduced visual acuity. Genome-wide homozygosity mapping followed by fine mapping defined a 830 Kb disease-associated locus (LOD score 3.5). Whole-exome sequencing identified a single missense mutation in the homozygosity region: c.95T>G, p.(Ile32Ser), in a conserved amino acid within the first predicted transmembrane domain of SLC38A8. The mutation fully segregated with the disease-associated phenotype, demonstrating an ∼10% carrier rate in Mumbai Jews. SLC38A8 encodes a putative sodium-dependent amino-acid/proton antiporter, which we showed to be expressed solely in the eye. Thus, a homozygous SLC38A8 mutation likely underlies isolated foveal hypoplasia.     

Educational lectures enhance knowledge about the human immunodeficiency virus (HIV) and reduce risky behavior and fear among methadone maintenance treatment patients

Abstract

Background: The aim of this study was to characterize human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related knowledge and stigma among methadone maintenance treatment (MMT) patients and evaluate the contribution of an educational lecture in reducing risky behavior and unjustified overprotective behavior due to fear and stigma among MMT patients. Methods: Patients from an MMT clinic within a tertiary medical center were invited to an educational lecture on HIV/AIDS. Seventy participants (of current 330) were chosen by a random sample (December 2015), plus at-risk patients and HIV patients. Attendee compliance and change in scores of questionnaires on knowledge (modified HIV-K-Q-22) and on sexual and injection behaviors were studied. Results: Forty-six patients (65.7% compliance) attended the lecture, and their knowledge and behavior scores improved 2?weeks post-lecture (knowledge: from 14.2?±?3 to 19.0?±?2.2 [P?<?.0005], sexual behavior: from 12.1?±?2.9 to 8.8?±?3.0 [P?<?.0005], and injection behavior: from 7.3?±?6.2 to 0.2?±?1.3 [P?<?.0005]). The unjustified fear of proximity to HIV carriers reported by 50% attendees fell to 35% post-lecture. Eight months post-lecture, the scores on knowledge and risky behavior of 21 randomly chosen attendees were still better than pre-lecture scores (knowledge: 15.4?±?2.3 vs. 17.2?±?1.8 [paired t test, P?=?.001], sexual behavior: 13.2?±?2.3 vs. 9.7?±?2.9 [P?<?.0005], and injection behavior: 9.3?±?5.6 vs. 2.8?±?3.1 [P?<?.0005]). Drug abuse and treatment adherence were not related to intervention and to risky behavior. Conclusions: More knowledge, less fear, and less risky behavior immediately and at 8?months post-lecture reflect the success and importance of the educational intervention. Future efforts are needed in order to reduce ignorance and fear associated with HIV/AIDS.