CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I-restricted T cell receptors (TcR) differentiate into CD8⁺ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8-null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I-restricted TcR. In all three instances CD8 was required for positive selection of MHC class I-restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I-restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I-restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.     

beta-endorphin is a potent analgesic agent.

beta-Endorphin, an opiate-like peptide, has potent antinociceptive properties when it is administered directly into the brain and assayed in the the tail-flick, hot-plate, and writhing tests in mice and in the wet shake test in rats. On a molar basis, beta-endorphin is 18 to 33 times more potent than morphine and its actions are blocked by the specific opiate antagonist, naloxone hydrochloride. The activity of beta-endorphin in vivo is also compared to other peptides that show opiate-like activity in assays in vitro.     

A useful alternative surgical technique to reconstructing large defects following excision of recurrent pilonidal sinus disease in the intergluteal region: An operative approach for the transverse lumbar artery perforator flap

The reconstruction of defects in the intergluteal region following pilonidal sinus excision is challenging due to its anatomical location, close proximity to the anus, and being a high‐tension area prone to wound‐healing problems. Excision and primary closure is known to carry a higher risk of recurrence and subsequent complications compared with using nearby local healthy tissue, such as a flap, to reconstruct defect. Extra due diligence should be given to patient selection and flap choice when deciding the reconstruction of a defect. The senior author, who has briefly reviewed complication rates in previous published literature, prefers the transverse lumbar artery perforator (TLAP) flap for reconstruction following pilonidal sinus excision in the intergluteal region. This paper illustrates the operative approach used by the senior author when raising a TLAP flap.     

Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study

In the National Heart, Lung and Blood Institute Type II Coronary Intervention Study, patients with Type II hyperlipoproteinemia and coronary artery disease (CAD) were placed on a low-fat, low-cholesterol diet and then were randomly allocated to receive either 6 g cholestyramine four times daily or placebo. This double-blind study evaluated the effects of cholestyramine on the progression of CAD as assessed by angiography. Diet alone reduced the low-density lipoprotein cholesterol 6% in both groups. After randomization, low-density lipoprotein cholesterol decreased another 5% in the placebo group and 26% in the cholestyramine-treated group. Coronary angiography was performed in 116 patients before and after 5 years of treatment. CAD progressed in 49% (28 of 57) of the placebo-treated patients vs 32% (19 of 59) of the cholestyramine-treated patients (p less than .05). When only definite progression was considered, 35% (20 of 57) of the placebo-treated patients vs 25% (15 of 59) of the cholestyramine-treated patients exhibited definite progression; the difference was not statistically significant. However, when this analysis was performed with adjustment for baseline inequalities of risk factors, effect of treatment was more pronounced. Of lesions causing 50% or greater stenosis at baseline, 33% of placebo-treated and 12% of cholestyramine-treated patients manifested lesion progression (p less than .05). Similar analyses with other end points (percent of baseline lesions that progressed, lesions that progressed to occlusion, lesions that regressed, size of lesion change, and all cardiovascular end points) all favored the cholestyramine-treated group, but were not statistically significant. Thus, although the sample size does not allow a definitive conclusion to be drawn, this study suggests that cholestyramine treatment retards the rate of progression of CAD in patients with Type II hyperlipoproteinemia.     

Differences in neuroplasticity after spinal cord injury in varying animal models and humans

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.     

The utility of adipose-derived stem cells and stromal vascular fraction for oncologic soft tissue reconstruction: Is it safe? A matter for debate

Autologous free-fat grafting (AFG) has emerged as an attractive proposition for soft-tissue reconstruction of various contour defects because it obviates more complex reconstructive options and reduces operative times and donor-site morbidity. Nonetheless, a common complication of this procedure is the resorption of the engrafted fat. Cell-assisted lipotransfer (CAL) is now a well-regarded technique where adipose-derived stem cell (ASC)-rich stromal vascular fraction is admixed with lipoaspirate, increasing the volumetric outcome of fat grafts in light of its potent angiogenic and adipogenic properties. Criticisms, however, remain regarding this modality especially for the treatment of post-oncologic defects. Laboratory data has attested to its propensity to perpetuate tumor cells as a result of its paracrine effects on the host microenvironment. This review article aims to present the underlying facts behind ASC therapy and provide meaningful discourse as to its utility in post-oncologic soft tissue reconstruction.