Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

In situ forming parenteral drug delivery systems: an overview.

Biodegradable injectable in situ forming drug delivery systems represent an attractive alternative to microspheres and implants as parenteral depot systems. Their importance will grow as numerous proteins will lose their patent protection in the near future. These devices may offer attractive opportunities for protein delivery and could possibly extend the patent life of protein drugs. The controlled release of bioactive macromolecules via (semi-) solid in situ forming systems has a number of advantages, such as ease of administration, less complicated fabrication, and less stressful manufacturing conditions for sensitive drug molecules. For these reasons, a number of polymeric drug delivery systems with the ability to form a drug reservoir at the injection site are under investigation. Here, we review various strategies used for the preparation of in situ forming parenteral drug depots and their potential benefits/draw-backs, especially with regard to the delivery of protein drug candidates.     

Deleterious effects of irradiation and bone marrow transplantation therapy in the genetically anemic an/an mouse

The efficacy and outcome of bone marrow transplantation therapy following lethal irradiation were examined in syngeneic mice that had a hereditary macrocytic anemia (an/an) or were genotypically normal (+/+). Successful RBC and WBC replacement, based on blood cell parameters and donor genetic markers, were observed in all combinations of transplant therapy. Nevertheless, the an/an mice died prematurely several months after treatment, whether they received +/+ or an/an marrow cells. In contrast, the +/+ recipients of either +/+ or an/an marrow cells survived for at least 1 year after transplantation. Premature death of the an/an mice was associated with lymphopenia, anemia, kidney lesions, and severe pathogen-free pneumonitis. On the basis of our results, we hypothesize that the premature deaths of an/an mice are caused by a kind of chronic irradiation damage to which an/an mice are especially susceptible.     

Surveillance of Creutzfeldt Jakob disease in the United Kingdom

By the end of May 2000, 54 definite cases and 13 probable cases of vCJD had been notified in the United Kingdom by the National CJD Surveillance Unit set up in 1990. All definite cases for whom data are available are methionine homozygous at codon 129 of     

Autoimmune neutropenia: clinical and laboratory studies in 143 patients

Summary Clinical and laboratory data of 143 patients with primary or secondary autoimmune neutropenia (AIN) were evaluated. Primary AIN was found predominantly in children below 3 years, whereas secondary AIN was more frequent in patients 40–60 years of age. Female patients with primary AIN were slightly more prevalent (54%) than male patients (46%). The peripheral blood count showed normal or diminished leukocyte counts with median absolute neutrophil counts of 250 cells/l. In 38% of the patients neutropenia was accompanied by monocytosis. Bone marrow examination revealed in 95% a normo- or hypercellular marrow with a marked reduction of mature neutrophils in 56% of the specimens. Twenty-three percent of the sera showed specificity for the NA1 antigen. Patients were usually affected by benign bacterial infections of the skin and of the upper respiratory tract, as well as by recurrent otitis media. Infections were treated symptomatically, and only six patients required continuous administration of antibiotics. Remission of neutropenia during treatment occurred in three of six patients treated with intravenous immunoglobulin G and in three of four patients who received steroid therapy. Except for one patient neutropenia relapsed after discontinuation of therapy. During a follow-up of 6–36 months, spontaneous remission has been observed in four patients.This work was supported by theDeutsche Forschungsgemeinschaft (Mu 277/9-7)     

Ganglion cyst of the foot treated with electroacupuncture: A case report

Objective:

To present the clinical management of a ganglion cyst presenting on the dorsolateral aspect of the foot.

Clinical Features:

A 45-year-old female cyclist complaining of ganglion cyst following training period.

Intervention and Outcome:

Patient was treated with high-frequency electroacupuncture in four consecutive sessions over four weeks, and reported resolution of the cyst following therapeutic intervention.

Conclusions:

Ganglion cysts of the foot are relatively rare connective tissue tumours with variable treatment approaches. Electroacupuncture may be a novel and non-invasive conservative approach for the treatment of ganglion cysts. Further evaluation of the efficacy of such treatment is warranted.     

The cytoskeleton in Chediak-Higashi syndrome fibroblasts

The Chediak-Higashi syndrome (CHS) trait is expressed in cultured human skin fibroblasts as an abnormal perinuclear concentration of moderately enlarged lysosomes. The cytoskeleton of CHS fibroblasts appears intact. Microtubules are normal in number and morphology, as assessed by colchicine binding studies, antitubulin immunofluorescence, and electron microscopy. Deformability by shear force is unaltered and microfilaments are abundant. However, CHS lysosomes appear to interact abnormally with the cytoskeleton, since the perinculear aggregation partially disperses after depolymerization of cell microtubules with colchicine. These results suggest that CHS is associated with a defect of either the lysosomal membrane itself or of lysosomal membrane- microtubule interaction.     

Rasch analysis of clinical outcome measures in spinal muscular atrophy

Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49 :422–430, 2014     

Effects of process and formulation parameters on characteristics and internal morphology of poly(d,l-lactide-co-glycolide) microspheres formed by the solvent evaporation method.

Taking ABT627 as a hydrophobic model drug, poly-(lactic-co-glycolic acid) (PLGA) microspheres were prepared by an emulsion solvent evaporation method. Various process parameters, such as continuous phase/dispersed phase (CP/DP) ratio, polymer concentration, initial drug loading, polyvinyl alcohol concentration and pH, on the characteristics of microspheres and in vitro drug release pattern of ABT627 were investigated. Internal morphology of the microspheres was observed with scanning electron microscopy by stereological method. CP/DP is a critical factor in preparing microspheres and drug loading increased significantly with increasing CP/DP ratios accompanied by a remarkably decreased burst release. At CP/DP ratio 20, microspheres with a core-shell structure were formed and the internal porosity of the microspheres decreased with increasing CP/DP ratio. Increase in PLGA concentration led to increased particle sizes and decreased drug release rates. ABT627 release rate increased considerably with increasing PVA concentrations in the continuous phase from 0.1% to 0.5%. The maximum solubility of ABT627 in PLGA was approximately 30%, under which ABT627 was dispersed in PLGA matrix in a molecular state. Increase in initial drug loading had no significant influence on particle size, drug encapsulation efficiency, burst release and internal morphology. However, drug release rate decreased at higher drug loading. Independent of process parameters, ABT627 was slowly released from the PLGA microspheres over 30 days, by a combination of diffusion and polymer degradation. During the first 13 days, ABT627 was mainly released by the mechanism of diffusion demonstrated by the unchanged internal morphology. In contrast, a core-shell structure of the microspheres was observed after being incubated in the release medium for 17 days, independent of drug loading, implying that the ABT627/PLGA microspheres degraded by autocatalytic effect, starting from inside of the matrix. In conclusion, hydrophobic drug release from the PLGA microspheres is mainly dependent on the internal morphology and drug distribution state in the microspheres.