Amphotropic or Gibbon Ape Leukemia Virus Retrovirus Binding and Transduction Correlates with the Level of Receptor mRNA in Human Hematopoietic Cell Lines

ABSTRACT: The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1). We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor. We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2). In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines. PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector. The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1α. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status.     

Echocardiographic analysis of ventricular septal dynamics in hypertrophic cardiomyopathy and other diseases

It has been suggested that the adynamic or hypokinetic appearance of the ventricular septum is a unique echocardiographic feature of hypertrophic cardiomyopathy (HC). To determine how characteristic of HC the adynamic septum is, 70 patients with this disease, and 31 with other cardiac diseases that produce left ventricular (LV) hypertrophy and pressure overload (aortic valvular stenosis or systemic hypertension), and 25 subjects with normal hearts were studied by echocardiography. On M-mode echocardiography, 53 of 70 patients (75%) with HC had an abnormally low value for percent systolic thickening of the septum associated with either reduced or normal septal excursion; however, 17 patients (25%) showed normal septal dynamics. Twenty of 31 patients (64%) with other cardiac diseases that produce pressure overload showed normal septal thickening and excursion, while 11 (36%) had reduced systolic thickening associated with either diminished or normal excursion. Greatly reduced values for percent systolic thickening of the septum were present both in patients with HC (13 +/- 1%) and in patients with other cardiac diseases (21 +/- 2%). However, differences in systolic septal thickening between the 2 groups were largely a manifestation of the greater absolute diastolic septal thickness in patients with HC. When values for percent systolic thickening were normalized for diastolic septal thickness, or when systolic thickening was compared in only patients with similar diastolic septal thicknesses, differences in septal thickening between patients with HC and those patients with other cardiac diseases were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human Cytomegalovirus and Epstein-Barr virus specific immunity in patients with ulcerative colitis

Clinical and Experimental Medicine - Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in...     

Does the autonomic nervous system contribute to the initiation and progression of prostate cancer？

In the July 12 issue of Science maga-zine, researchers from the AlbertEinstein College of Medicine, the Mount Sinai School of Medicine, the Durham VA Medical Centre and Duke University published an elegant study demonstrating that the sym-pathetic nervous system, acting through β2 and β3-adrenoceptors in the prostate, plays an important role in the initiation of prostate can-cer, while the parasympathetic nervous system plays a role in the dissemination of tumour metastases via M1 muscarirdc receptors. These findings are significant because they indicate that receptors associated with the autonomic nervous system may be viable tar-gets for prostate cancer therapy.     

Triple-V flap: nipple reconstruction using a modified C-V flap technique for long-lasting improvement of projection

Background

Reconstruction of the nipple–areola complex is the last procedure in breast reconstruction after mastectomy. Various techniques have been described, but the creation of a long-lasting projection represents a challenge in plastic surgery causing frequent nipple projection loss.

Methods

From December 2008 and September 2010, we performed 43 nipple reconstructions using our new technique named “triple-V flap.” This procedure is similar to C-V flap but uses a further V limb area that is de-epithelialized and provides significant support to the new nipple. Clinical assessment was performed with a caliper measuring nipple projection at 1, 6, and 12 months after the surgical procedure.

Results

We evaluated the triple-V nipple reconstruction technique in 43 patients. Reconstructed nipple projection ranged between 3.3 and 6.4 mm (mean 4.8 mm). Mean decrease in nipple projection was 0.2 mm at 1 month, 1.4 mm at 6 months, and 1.6 mm at 1 year. After 1 year, mean nipple projection decrease was 34 %.

Conclusions

Our triple-V technique allows the maintenance of long-lasting projection of the reconstructed nipple at 12 months after surgery. Ease and speed of execution made our technique usable in all patients who need to complete the breast reconstruction process. Level of Evidence: Level IV, therapeutic study.     

Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs

Recent studies have shown that ultrasound (US)-mediated transdermal drug delivery offers a promising potential for noninvasive drug administration. The purpose of this study was to improve low-frequency (20 kHz) US methods for enhancing the transport of insulin in vitro across human skin. The feasibility of using US produced by small, lightweight novel transducers was explored for enhancing the transport of insulin across skin. Previous investigators have used US devices such as large, heavy sonicators or commercially obtained transducers for this type of research. The experiments carried out in this study used two low-profile novel US transducer arrays, the stack and standard array, for improved transport of insulin. The stack array generated a spatial peak temporal peak intensity (I(SPTP)) of 15.4 +/- 0.6 mW/cm(2) and the standard array had an I(SPTP) of 173.7 +/- 1.2 mW/cm(2). Spectrophotometeric absorption techniques were used for determining insulin transport in vitro across human skin. Compared with passive transmission (4.1 +/- 0.5 U) over an exposure period of 1 h, the standard array facilitated over a sevenfold increase in the noninvasive transdermal transport of Humulin R insulin (45.9 +/- 12.9 U). Using Humalog insulin with the standard array, there was a fourfold increase in the US-facilitated transmission over that in the control. These promising results indicate that low-frequency US can be used in a practical device for enhanced transport across the stratum corneum.     

Results obtained with level II oncoplastic surgery spanning 20 years of breast cancer treatment: Do we really need further demonstration of reliability?

Oncoplastic surgery (OPS) has demonstrated its superiority above traditional breast conserving surgery, but is still struggling to consolidate its role in breast cancer therapeutic protocols mainly because of contrasting scientific evidences and reduced follow‐up results available. The objective of our contribution is to analyze results obtained with 381 patients consecutively treated in our Multidisciplinary Breast Center by means of level II OPS between January 1998 and January 2018 for unilateral, primary breast cancer. Surgical endpoints were mean specimen weight and volume, mean diameter of main lesion (MLD), rates of positive margins (PMR), re‐excision (RR), conversion to mastectomy (CMR), complications (CR) and oncological endpoints as overall survival (OS), disease‐free survival (DFS), and local recurrence rate (LR). About 29.1% were treated for multifocal/multicentric disease, and 29.1% previously underwent neo‐adjuvant chemotherapy (NACT). Regarding surgical techniques, 53.0% of patients received “inverted T” and 30.1% “J” mammoplasties, whereas 13.6% underwent “round block,” 2.3% “Grisotti,” and 1% “batwing” techniques. Regarding surgical outcomes, mean specimen weight was 215 g (50‐2157) and volume 345 mm³ (21‐7980). MLD 23 mm, PMR 7.6%, RR 3.6%, CMR 1.6%, and CR 5.8%. With a mean follow‐up of 118 months, oncological outcomes were: OS 93.7%, DFS 82.3%, LR 4.4%. In conclusion, our analysis confirmed level II OPS reliability even for longer follow‐up timing and in difficult situations as multifocal disease or after NACT.