NG2+ glial cells: a novel glial cell population in the adult brain

We describe a major glial cell population in the central nervous system (CNS) that can be identified by the expression of 2 cell surface molecules, the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alphaR). In vitro and in the developing brain in vivo, NG2 and PDGF alphaR are expressed on oligodendrocyte progenitor cells but are down-regulated as the progenitor cells differentiate into mature oligodendrocytes. In the mature CNS, numerous NG2+/PDGF alphaR+ cells with extensive arborization of their cell processes are found ubiquitously long after oligodendrocytes are generated. NG2+ cells in the mature CNS do not express antigens specific to mature oligodendrocytes, astrocytes, microglia, or neurons, suggesting that they are a novel population of glial cells. Recently NG2+ cells in the adult CNS have been shown to undergo proliferation and morphological changes in response to a variety of stimuli, such as demyelination and inflammation, suggesting that they are dynamic cells capable of responding to changes in the environment. Furthermore, high levels of NG2+ and PDGF alphaR are expressed on oligodendroglioma cells, raising the possibility that the NG2+/PDGF alphaR+ cells in the mature CNS contribute to glial neoplasm.     

A case of effective combination therapy with docetaxel, cyclophosphamide and trastuzumab as primary systemic therapy for locally advanced HER2-positive breast cancer

We experienced a case of locally advanced breast cancer achieving a significant improvement by using a combination of docetaxel(DOC), cyclophosphamide(CPA)and trastuzumab as a primary systemic therapy.The patient was a 54-year-old woman suffering from a right breast mass, who was referred to our hospital and diagnosed with HER2-positive breast cancer with subclavicular lymph nodes metastases.The combination therapy of DOC(75 mg/m / 2), CPA(600 mg/m2)and trastuzumab(loading dose 8 mg/kg, then 6 mg/kg)for 6 courses at q3 week intervals, was started as the primary systemic therapy. After 6 courses of treatment, a right modified radical mastectomy was performed.There were a little breast cancer cells in the breast, and no axillary lymph node metastases.The combination chemotherapeutic regime with DOC, CPA and trastuzumab seems to be useful for treatment of HER2-positive breast cancer.     

Use of positron emission tomography to measure the effects of nalmefene on D1 and D2 dopamine receptors in rat brain

Positron emission tomography (PET) has been used in humans and in non-human primates to image and measure radioligand binding to neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, nalmefene, on the binding activity of [¹¹C]SCH23390 and [¹¹C]N-methylspiperone at D₁ and D₂ dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague–Dawley rats received either a single injection of 10 mg/kg of nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of nalmefene, the binding potential of [¹¹C]SCH23390 in the striatum was significantly increased. No changes in [¹¹C]N-methylspiperone binding were found. Following chronic nalmefene administration, no significant change in either [¹¹C]SCH23390 binding potential or [¹¹C]N-methylspiperone binding was detected. These results suggest that nalmefene administration produces transient changes in the binding potential of D₁-receptors in the striatum that are normalized after 1 week of steady-state administration.     

Clinical Imaging of Bone Microarchitecture with HR-pQCT

Osteoporosis, a disease characterized by loss of bone mass and structural deterioration, is currently diagnosed by dual-energy x-ray absorptiometry (DXA). However, DXA does not provide information about bone microstructure, which is a key determinant of bone strength. Recent advances in imaging permit the assessment of bone microstructure in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT). From these data, novel image processing techniques can be applied to characterize bone quality and strength. To date, most HR-pQCT studies are cross-sectional comparing subjects with and without fracture. These studies have shown that HR-pQCT is capable of discriminating fracture status independent of DXA. Recent longitudinal studies present new challenges in terms of analyzing the same region of interest and multisite calibrations. Careful application of analysis techniques and educated clinical interpretation of HR-pQCT results have improved our understanding of various bone-related diseases and will no doubt continue to do so in the future.     

Clinical Tools to Evaluate Bone Strength

Although dual-energy absorptiometry (DXA) has proven its clinical utility, there are many limitations to using areal bone mineral density (aBMD) measured by DXA to predict bone strength and fracture risk. Recent advances in imaging techniques including quantitative computed tomography (QCT) and magnetic resonance imaging (MRI) have led to non-invasive assessment of bone macro-architecture and micro-architecture. Analysis techniques such as finite element (FE) modelling use image data to estimate the ability of a bone to carry load, and provide new insight into treatment effects and fracture risk. QCT and MRI can image clinically relevant sites such as the lumbar spine and proximal femur. High-resolution peripheral QCT (HR-pQCT) offers superior resolution at peripheral sites including the radius and tibia. Measures obtained from QCT and HR-pQCT have been significantly associated with fracture risk independently of DXA-derived parameters. FE models derived from QCT, HR-pQCT, and MRI are capable of detecting treatment-induced changes in bone strength, and preliminary results suggest that QCT and HR-pQCT-derived FE models can discriminate fracture cases from controls. Continued advances in image acquisition and analysis will improve our ability to predict fracture and to understand factors associated with bone strength.     

A case of primary ciliary dyskinesia treated with ICSI using testicular spermatozoa: case report and a review of the literature

PurposeTo investigate whether or not intracytoplasmic sperm injection (ICSI) using spermatozoa extracted from testis (TESE‐ICSI) is a more effective treatment than ICSI with ejaculated spermatozoa (EJ‐ICSI) for primary ciliary dyskinesia (PCD).MethodsWe reported a case of PCD in which we performed TESE‐ICSI after repeated failure of EJ‐ICSI. Together with data from previous case reports, we compared the fertilization rate and pregnancy outcome of TESE‐ICSI and EJ‐ICSI.ResultsIn our case, TESE‐ICSI improved the morphology of spermatozoa and fertilization rate. However, the outcome was only a biochemical pregnancy. According to the analysis combined with previous reports, there was no difference in the fertilization rate and pregnancy outcome parameters between TESE‐ICSI and EJ‐ICSI.ConclusionsTESE‐ICSI for PCD may improve the fertilization rate compared to EJ‐ICSI. However, it does not necessarily improve the pregnancy outcome for a patient with primary ciliary dyskinesia.     

Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery

Polyplex micelles formed with plasmid DNA (pDNA) and poly(ethylene glycol) (PEG)-block-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] exhibit effective endosomal escaping properties based on di-protonation of diamine side chains with decreasing pH, which improves their transfection efficiency and thus are promising candidates for local in vivo gene transfer. Here, PEG-PAsp(DET) polyplex micelles were further improved as in vivo systemic vectors by introduction of cholesterol (Chole) into the ω-terminus of PEG-PAsp(DET) to obtain PEG-PAsp(DET)-Chole. Introduction of the cholesterol resulted in enhanced association of block copolymers with pDNA, which led to increased stability in proteinous medium and also in the blood stream after systemic injection compared to PEG-PAsp(DET) micelles. The synergistic effect between enhanced polymer association with pDNA and increased micelle stability of PEG-PAsp(DET)-Chole polyplex micelles led to high in vitro gene transfer even at relatively low concentrations, due to efficient cellular uptake and effective endosomal escape of block copolymers and pDNA. Finally, PEG-PAsp(DET)-Chole micelles achieved significant suppression of tumor growth following intravenous injection into mice bearing a subcutaneous pancreatic tumor using therapeutic pDNA encoding an anti-angiogenic protein. These results suggest that PEG-PAsp(DET)-Chole micelles can be effective systemic gene vectors for treatment of solid tumors.