Transition of polycythemia vera to chronic neutrophilic leukemia

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.     

Influence of age and sex on signal intensities of the posterior lobe of the pituitary gland on T1-weighted images from 3 T MRI

Purpose

To elucidate the influence of age and sex on the signal intensity (SI) of the posterior lobe of the pituitary gland (PPG) on T1-weighted images (T1WI) from 3 T MRI.

Materials and methods

Sagittal T1WI acquired from three-dimensional fast spoiled gradient recalled acquisition in the steady state in 1,634 subjects without conditions affecting antidiuretic hormone were evaluated retrospectively. The presence or absence of a bright signal in the PPG was assessed qualitatively. The SI ratio of the PPG to the pons (SIR) was obtained from quantitative measurements. We statistically analyzed these data, creating 14 subject groups categorized according to age and sex, and applied a Poisson generalized linear model to the SIR data.

Results

The characteristic bright signal was absent in 47 subjects (2.8 %), with no significant difference in incidence among the groups. The SIR was inversely related to age in both males (r > 0.7) and females (r > 0.9), and was significantly higher in females in the third to the eighth decades (p < 0.05). Analysis of the whole SIR dataset using a generalized linear model showed that the estimated SIR decreased by 1.7 % per decade and is higher in females.

Conclusion

Age and sex influence the SI of the PPG on T1WI. These findings may aid the recognition of PPG signal abnormalities on T1WI.     

Results of intravitreal triamcinolone acetonide in patients with macular edema secondary to branch retinal vein occlusion

Background Macular edema is one of the most common causes of visual loss in patients with retinal vein oclusions. Intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factors are modalities of treatment for macular edema secondary to branch retinal vein occlusion (BRVO). Objective To present the results of intravitreal triamcinolone acetonide therapy in patients with macular edema secondary to BRVO. Setting A retrospective clinical interventional study included 32 patients with macular edema secondary to BRVO. Method The records of 32 eyes of 32 patients who received 4 mg/0.1 mL injection of intravitreal triamcinlone for macular edema secondary to BRVO were evaluated. Patients with visual acuity <0.40 logMAR (logarithm of the minimum angle of resolution), central macular thickness (CMT) >260 μm and no neovascularization at baseline were included. Patients with diabetes mellitus, a history of intravitreal anti vascular endothelial growth factor injection, grid laser photocoagulation and ischemic BRVO were excluded. The re-injections were performed in cases with increased CMT >100 μm or vision loss of five or more letters. Results The mean follow-up was 12 ± 1.9 months. The visual acuity increased from 0.58 ± 0.16 at baseline to 0.25 ± 0.11 logMAR (P < 0.001). The CMT decreased from 490 ± 107 μm at baseline to 266 ± 90 μm at 12 months (P < 0.001). Both cataract and glaucoma developed in 18.75 % patients. Conclusion Intravitreal triamcinolone, due to absence of systemic side effects, can be used with confidence for treatment macular edema secondary to BRVO. However the main disadvantages of intravitreal triamcinolone injection are elevation of intraocular pressure and formation of cataract.     

Polyplex Micelles from Triblock Copolymers Composed of Tandemly Aligned Segments with Biocompatible, Endosomal Escaping, and DNA-Condensing Functions for Systemic Gene Delivery to Pancreatic Tumor Tissue

Purpose  For systemic gene delivery to pancreatic tumor tissues, we prepared a three-layered polyplex micelle equipped with biocompatibility, efficient endosomal escape, and pDNA condensation functions from three components tandemly aligned; poly(ethylene glycol) (PEG), a poly(aspartamide) derivative with a 1,2-diaminoethane moiety (PAsp(DET)), and poly(l-lysine). Materials and Methods  The size and in vitro transfection efficacy of the polyplex micelles were determined by dynamic light scattering (DLS) and luciferase assay, respectively. The systemic gene delivery with the polyplex micelles was evaluated from enhanced green fluorescence protein (EGFP) expression in the tumor tissues. Results  The polyplex micelles were approximately 80 nm in size and had one order of magnitude higher in vitro transfection efficacy than that of a diblock copolymer as a control. With the aid of transforming growth factor (TGF)-β type I receptor (TβR-1) inhibitor, which enhances accumulation of macromolecular drugs in tumor tissues, the polyplex micelle from the triblock copolymer showed significant EGFP expression in the pancreatic tumor (BxPC3) tissues, mainly in the stromal regions including the vascular endothelial cells and fibroblasts. Conclusion  The three-layered polyplex micelles were confirmed to be an effective gene delivery system to subcutaneously implanted pancreatic tumor tissues through systemic administration.     

Intracellular internalization mechanism of protein transfection reagents

A protein transfection reagent is a powerful tool for elucidating a protein function in a cell, and plays an important role in the fields of cell biology and drug discovery. Many researchers have developed protein delivery systems and several systems are commercially available. In this study, we focus on the biological functions of three commercially available protein transfection reagents, Pro-DeliverIN, Xfect, and TurboFect, especially in their internalization routes by HeLa cells. A cellular uptake study using specific endocytosis inhibitors and confocal laser scanning microscope observation revealed that each reagent was internalized into HeLa cells by different mechanism. It is our hope that the results presented here will help in the choice and use of protein transfection reagents for experiments.     

Extent of hypophagia caused by propionate infusion is related to plasma glucose concentration in lactating dairy cows

Two experiments were conducted to evaluate how dose-response effects of intraruminal infusion of propionate on feeding behavior and plasma metabolites are altered by diets differing in fermentability. Twelve ruminally cannulated Holstein cows were used in each experiment. Cows were fed diets containing either steam flaked corn or dry cracked corn (30% of dietary dry matter) in expt. 1, and diets differing in forage-to-concentrate ratio (66:34 vs. 36:64) in expt. 2. For both experiments, the experimental design was a crossover for dietary treatment, and a 6 x 6 Latin square for infusion treatment within a diet for each period. Infusion treatments were mixtures of sodium propionate and sodium acetate, containing propionate at 0, 0.2, 0.4, 0.6, 0.8 and 1.0 as a fraction of total volatile fatty acids infused. Treatment solutions were infused into the rumen continuously for 18 h starting 6 h before feeding at a rate of 23.1 mmol/min. Although propionate production from ruminal fermentation was expected to be different, dietary treatments did not affect dry matter intake (DMI) responses to propionate infusion for either experiment. However, propionate infusion decreased DMI linearly in expt. 1, but did not decrease DMI at lower rates of propionate infusion, which were much more effective at increasing plasma glucose concentration in expt. 2. Propionate had a smaller hypophagic effect at low concentrations of plasma glucose and had a greater hypophagic effect at elevated concentrations of plasma glucose, which could be explained by changes in the metabolism of propionate in the liver.     

Soy product consumption and the risk of colon cancer: a prospective study in Takayama, Japan

The relationship of the intake of soy products and the incidence of colon cancer was prospectively evaluated in a population-based cohort study in Japan. The total intake of soy products and isoflavones in a daily diet was estimated from a validated questionnaire administered at the baseline. The participation rate of the questionnaire was 92.0%. The participants were followed from 1992 to 2000, and colon cancer diagnoses were identified at the main hospitals in the study area. In the analysis, 13,894 men and 16,327 women were included. The medians for energy-adjusted soy product intake were 85.52 g/day for men and 79.60 g/day for women. During follow-up, 111 men and 102 women were diagnosed with colon cancer. A Cox-proportional hazard model was applied to assess the risk of colon cancer incidence. Among women, the risk was reduced with an increased soy product consumption; the hazard ratio in the highest tertile was 0.56 (95% CI 0.34-0.92) compared as the lowest tertile (trend: P=0.04), after adjusting for multiple potential confounders. Among men, no significant association was observed. Our results exhibited the weak benefit of soy foods only among women. Further research to confirm our results may be beneficial.     

Strain differences in the responsiveness between Sprague-Dawley and Fischer rats to nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor

To determine a rat strain appropriate for carcinogenicity testing of FYX-051, a xanthine oxidoreductase inhibitor, we performed a 4-week oral toxicity study by administering 0.3, 1 and 3 mg/kg, and 1, 3 and 10 mg/kg of FYX-051 to male Sprague-Dawley (SD) and Fischer (F344) rats, respectively. Histopathology revealed that the degree of FYX-051-induced nephropathy was 3-fold stronger in SD rats than in F344 rats. Our previous study demonstrated that the key factor of species differences in FYX-051-induced nephropathy is purine metabolism. This observation led us to examine the involvement of purine metabolism in differences among two strains of rats. However, purine metabolism was proven not to be implicated as an important factor. Subsequently, other factors responsible for the strain differences were examined. FYX-051-induced increases in plasma xanthine concentrations were higher in SD rats than in F344 rats, suggesting more remarkable effects on pharmacodynamics in the former than the latter. Urinary volume was greater in F344 rats administered 10 mg/kg of FYX-051 (6.8 ml/h/kg) than in SD rats administered 3 mg/kg of FYX-051 (5.0 ml/h/kg), implying easier xanthine excretion in the former. Urinary xanthine solubility was 55 mg/dl in F344 rats aged 6 weeks, in contrast to 38 mg/dl in SD rats of the same age. Also, there were no significant differences in exposure levels at the same dose between SD and F344 rats. The outcomes of exposure levels and renal histopathology in both rats suggest the possibility that F344 rats could be exposed to a 3-fold higher amount of drug than SD rats in a carcinogenicity bioassay. The present study, therefore, suggested that strain differences of nephrotoxicity were caused by the combined effects of pharmacodynamics, xanthine excretion capacity, and urinary xanthine solubility. Furthermore, these results indicate that F344 rats would be a suitable strain for the carcinogenicity study of FYX-051.     

Tributyltin-binding protein type 1 has a distinctive lipocalin-like structure and is involved in the excretion of tributyltin in Japanese flounder, Paralichthys olivaceus

Tributyltin-binding protein type 1 (TBT-bp1) is a newly discovered protein that binds with TBT in the blood of the Japanese flounder, Paralichthys olivaceus. We determined the genomic sequence of TBT-bp1 and found that this protein has a conserved exon–intron structure that is common to the lipocalin protein family. The secondary and tertiary structures of TBT-bp1, predicted from amino acid sequence, included at least two α-helices and eight β-sheets that are conserved in all lipocalins and form a barrel structure that may bind with ligands. Analysis of the gene structure, secondary structure, and tertiary structure demonstrated that TBT-bp1 could be classified as a lipocalin. A homology search revealed the presence of TBT-bp1-like proteins in eight species of teleost. When flounder were injected intraperitoneally with TBT-d27 at 11.6 μg/fish, TBT-d27 was detected in the blood and in the skin mucus. The concentration of TBT-d27 in mucus was approximately 1/100 of that in the serum. Western blotting analysis revealed that TBT-bp1 was present in the skin mucus. These results suggest that TBT-bp1 in Japanese flounder binds with TBT and is excreted from the body via the mucus.     

Does a laparoscopic approach attenuate the body weight loss and lean body mass loss observed in open distal gastrectomy for gastric cancer? a single-institution exploratory analysis of the JCOG 0912 phase III trial

Background

Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer may prevent the loss of body weight and lean body mass resulting from reduced surgical stress in comparison to open distal gastrectomy (ODG). A multicenter phase III trial conducted by the Japan Clinical Oncology Group (JCOG0912 trial) was performed to confirm the non-inferiority of LADG to ODG for stage I gastric cancer in terms of relapse-free survival.

Methods

This study was performed as a single-institution exploratory analysis using the data of the patients from our hospital who were enrolled in the JCOG0912 phase III trial. Body weight and lean body mass were evaluated using a bioelectrical impedance analyzer within 1 week before and at 1 week, 1 month, and 3 months after surgery.

Results

One-hundred six patients were randomized to undergo ODG (54 patients) or LADG (51 patients). Body weight loss at 1 week, 1 month, and 3 months was ?3.0%, ?4.9%, and ?5.4%, respectively, in the ODG group and ?2.7%, ?4.3%, and ?5.7%, respectively, in the LADG group; the differences were not statistically significant (p = 0.330, 0.166, and 0.656, respectively). Lean body mass loss at 1 week, 1 month, and 3 months was ?2.8%, ?4.1%, and ?2.3%, respectively, in the ODG group and ?2.7%, ?2.9%, and ?3.0%, respectively, in the LADG group; the differences were not statistically significant (p = 0.610, 0.413, and 0.925, respectively).

Conclusions

The laparoscopic approach did not attenuate the loss of body weight and lean body mass in comparison to patients who underwent open distal gastrectomy for gastric cancer.