1141610241Altered expression of HuR, an mRNA stabilizing protein, mediates aberrant Placenta Growth Factor (PlGF) expression in preeclampsia

Background:  Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods:  Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results:  Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions:  HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects.     

Contributions of the ubiquitin–proteasome pathway and apoptosis to human skeletal muscle wasting with age

The primary mechanism that contributes to decreasing skeletal muscle strength and size with healthy aging is not presently known. This study examined the contribution of the ubiquitin–proteasome pathway and apoptosis to skeletal muscle wasting in older adults (n = 21; mean age = 72.76 ± 8.31 years) and young controls (n = 21; mean age = 21.48 ± 2.93 years). Subjects underwent a percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3) individual fiber type and cross-sectional area. In addition, a whole muscle strength test was also performed. A one-way ANOVA revealed significant increases in the number of positive TUNEL cells in older adults (87%; p < 0.05), although no significant increase in caspase-3/7 activity was detected. Additionally, ubiquitin ligase gene expression, individual muscle fiber type and CSA were not different between old and young subjects. Muscle strength was also significantly lower in old compared to young subjects (p < 0.05). In conclusion, this study indicates a preferential role for apoptosis contributing to decreases in muscle function with age.     

Visual processing in scotomata

Summary In contrast with other animals, when the occipital cortex is damaged in man, blindness occurs in spite of intact retinal projections to subcortical centers in the midbrain. By a proper selection of stimuli and responses, however, it can be shown that some information about the visual stimulus may be processed in regions of cortical blindness, even though the stimulus is not seen. One striking example of such processing occurs when dark, rather than bright flashes of light are presented in the scotoma. In this case the dark bars may actually be discriminated better in the scotoma than they are in the intact portion of the visual field. The nature of the residual discrimination has the properties of a primitive stereoscopic mechanism that ignores the sign of the stimulus disparity.     

Uniform safety of beating heart surgery using the octopus tissue stabilization system

BACKGROUND AND PURPOSE: Minimally invasive coronary artery bypass grafting (CABG) has been facilitated by the introduction of the Octopus Tissue Stabilization system (OTS). OTS improves exposure immobilizing the heart with minimal hemodynamic effects allowing multivessels off cardiopulmonary bypass (CPB) CABG. The purpose of this study was to compare the utilization and clinical outcome of the OTS in three geographically distinct centers. METHODS: 239 patients who underwent OTS-CABG at Allegheny University Hospital/Medical College of Pennsylvania, Harrisburg Hospital, and Park Nicollet Clinic/HealthSystem Minnesota were reviewed. Age, acuity of patients, and number and type of vessels bypassed were recorded. Complications, mortality, length of hospital stay, incidence of conversion to CPB and blood transfusions, and operating room costs were compared to risk matched control patients who underwent CPB CABG during the same period. RESULTS: Results were similar in all three centers. The average age was 62.3 years. Emergent operation was necessary in 7%-10% of patients, the operations averaged 1.8 grafts/patient. Arteries bypassed were LAD, DIAG, OM, RCA, PDA, and RPLB. There were 96% of operations completed without CPB. Morbidity was low (12%). Atrial fibrillation and blood transfusion rate were decreased. Mortality was 0 compared with a predicted mortality of 1.6%. Hospital length of stay was shorter and operating room costs were 61% lower. CONCLUSIONS: OTS provides predictable reproducible immobilization allowing the performance of single and multiple off-pump CABG to almost all coronary branches with minimal morbidity and decreased costs in a variety of patients. Similar findings from three different centers suggests that these results are easily reproducible.     

Seizures and civilian head injuries

Although several studies have reported on the risk of "early seizures" (seizures occurring within 7 days following a head injury), the reported proportions of patients experiencing these seizures vary from 1.4 to 15%. This wide divergence may be due to problems with methodology such as case selection and definitions of head injury and early seizures. In a series of 702 patients admitted with a head injury to Cook County Hospital (CCH), Chicago, Illinois, 29 (4.1%) had early seizures. This proportion is twice as high as one previously reported in a comparable series. This may reflect an actual difference between the two series or a case selection bias serving to elevate the proportion of patients with early seizures at CCH.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Causes of re-recurrence after polytetrafluoroethylene patch saphenoplasty for recurrent varicose veins

BACKGROUND: The aim of this study was to determine whether a polytetrafluoroethylene (PTFE) patch sutured over the religated saphenofemoral junction could reduce the rate of recurrence after operation for recurrent varicose veins. METHODS: Fifty patients who had surgery for recurrent long saphenous incompetence (81 legs had a small PTFE patch sutured over the religated saphenofemoral junction. There were no major complications following surgery. Three patients had a wound infection or delayed healing. All patients were invited for clinical examination and duplex imaging at a median of 19 (range 6-39) months after operation. RESULTS: Some 38 of 43 patients (70 legs) remained satisfied with the results of surgery; 16 (23 per cent) of 70 legs had visible veins on inspection and eight of these (11 per cent) involved symptomatic recurrence. Duplex imaging showed that recurrence was due to saphenofemoral junction incompetence in ten legs; two appeared to have a major groin connection but the other eight appeared to have neovascularization. Other causes were thigh perforator reflux (three legs) and cross-groin collaterals (three). Eleven of the 16 legs with recurrence had varicography but in two the procedure was a technical failure. Two legs had evidence of a significant connection (more than 3 mm) and two a minor connection (less than 3 mm) to the femoral vein at the level of the PTFE patch, but in the remainder recurrence was due to upper thigh perforating veins. There was good concordance between duplex imaging and varicography. CONCLUSION: PTFE patch saphenoplasty appears to be safe. Although these are early results, the technique seems potentially as effective as other barrier methods that have been investigated; in ten legs (12 per cent) recurrence was attributed to failure at the level of the PTFE patch.     

The Value of Ultrasound in Detecting Extra‐Axillary Regional Node Involvement in Patients With Advanced Breast Cancer

Assessment of the regional lymphatics is important for accurate staging and treatment of breast cancer patients. We sought to determine the role of regional ultrasound in providing clinically relevant information. We retrospectively analyzed data from patients who were treated curatively in 1996–2006 at The University of Texas MD Anderson Cancer Center for clinical stage III breast cancer. We compared differences in regional lymph node staging based on ultrasound versus mammography and physical examination in the 865 of 1,200 patients who had external-beam radiation as part of their treatment and regional ultrasound studies as part of their initial evaluation. Ultrasound uniquely identified additional lymph node involvement beyond the level I or II axilla in 37% of the patients (325 of 865), leading to a change in clinical nodal stage. Ninety-one percent of these abnormalities that could be biopsied (266 or 293) were confirmed to contain disease. The sites of additional regional nodal disease were: infraclavicular disease, 32% (275 of 865); supraclavicular disease, 16% (140 of 865); and internal mammary disease, 11% (98 of 865). All patients with involvement in the extra-axillary regional nodal basins received a radiation boost to the involved areas ≥10 Gy. Thus, over one third of patients with advanced breast cancer had their radiation plan altered by the ultrasound findings. Regional ultrasound evaluation in patients with advanced breast cancer commonly revealed abnormalities within and beyond the axilla, which changed the clinical stage of disease and the radiation treatment strategy. Therefore, regional ultrasound is beneficial in the initial staging evaluation for such patients.