Secure and effective gene delivery system of plasmid DNA coated by polynucleotide

Polynucleotides are anionic macromolecules which are expected to transfer into the targeted cells through specific uptake mechanisms. So, we developed polynucleotides coating complexes of plasmid DNA (pDNA) and polyethylenimine (PEI) for a secure and efficient gene delivery system and evaluated their usefulness. Polyadenylic acid (polyA), polyuridylic acid (polyU), polycytidylic acid (polyC), and polyguanylic acid (polyG) were examined as the coating materials. pDNA/PEI/polyA, pDNA/PEI/polyU, and pDNA/PEI/polyC complexes formed nanoparticles with a negative surface charge although pDNA/PEI/polyG was aggregated. The pDNA/PEI/polyC complex showed high transgene efficiency in B16-F10 cells although there was little efficiency in pDNA/PEI/polyA and pDNA/PEI/polyU complexes. An inhibition study strongly indicated the specific uptake mechanism of pDNA/PEI/polyC complex. Polynucleotide coating complexes had lower cytotoxicity than pDNA/PEI complex. The pDNA/PEI/polyC complex showed high gene expression selectively in the spleen after intravenous injection into mice. The pDNA/PEI/polyC complex showed no agglutination with erythrocytes and no acute toxicity although these were observed in pDNA/PEI complex. Thus, we developed polynucleotide coating complexes as novel vectors for clinical gene therapy, and the pDNA/PEI/polyC complex as a useful candidate for a gene delivery system.     

Partial tarsal arthrodesis for rheumatoid feet

Partial intertarsal joint arthrodesis was performed on 12 feet of 11 patients as a surgical treatment for planovalgus deformity of the foot and lesions of the intertarsal joints caused by rheumatoid arthritis. Single arthrodesis was performed on the talocalcaneal joint in eight feet, two of which underwent simultaneous total ankle arthroplasty, and on the talonavicular joint in two feet. Double arthrodesis was done on the talocalcaneal and talonavicular joints in one foot and on the talonavicular and calcaneocuboid joints in one foot. Screws or staples were used for fixation. Patients were followed for 2 years to 8 years 7 months (average 4 years 3 months). Osseous fusion was achieved in all feet, and satisfactory pain relief was obtained in all cases except one. We performed this surgery in patients who were relatively active, and the results indicated that arthrodesis of a small number of joints that caused pain and deformity was effective in reducing pain and correcting the deformity. We concluded that partial tarsal arthrodesis should be performed on a limited number of joints during the early stages of planovalgus deformity of the foot because more joints are found to be fixed during the advanced stages. However, progression of the osteoarthritis was found in the neighboring joints. Close follow-up observation is needed.     

Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan

Journal of Gastroenterology - Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of...     

Conjugated oestrogen during the menstrual cycle measured by a direct radioimmunoassay with an antiserum prepared against oestradiol-17-glucosiduronate-[C-6]-BSA conjugate

Early morning and 24 h urine samples and serum were collected daily throughout the menstrual cycle in women. Urinary oestradiol-17-glucosiduronate (E2-17-G) was measured with a direct radioimmunoassay whose antiserum had been prepared against E2-17-G-[C-6]-bovine serum albumin conjugate and was very specific. On the average, E2-17-G in early morning and 24 h urine samples showed a prominent peak one day before the peak of urinary LH. The time relationship between these urinary E2-17-G and serum E2 levels and peaks was also investigated.     

Short-Term and Long-Term Effects of Low-Density Lipoprotein (LDL) Apheresis on Restenosis after Percutaneous Transluminal Coronary Angioplasty (PTCA): Is Lowering Lp(a) by LDL Apheresis Effective on Restenosis after PTCA?

Abstract: It has been reported that serum lipoprotein(a) (Lp[a]) levels in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) were significantly higher than in patients without restenosis. In this study, we evaluated the preventive effect of LDL apheresis on restenosis after PTCA in patients with hypercholesterolemia. For 10 patients who had shown a serum cholesterol level of more than 220 mg/dl despite treatment with antihypercholesterolemic drugs, LDL apheresis was conducted every 2 weeks after a successful PTCA until restenosis could be checked. In 4 patients, LDL apheresis was conducted for 2 years. LDL apheresis significantly reduced serum cholesterol from 248 ± 22 mg/dl to 135 ± 26 mg/dl and Lp(a) from 42 ± 34 mg/dl to 21 ± 16 mg/dl. The average degree of stenosis in the 11 lesions undergoing PTCA was 92 ± 6% before PTCA, 35 ± 10% immediately after PTCA, and 38 ± 19% at 3 to 4 months after PTCA. Restenosis was observed in only 1 lesion. In 4 patients who received LDL apheresis for 2 years, restenosis did not occur in any of the 4 lesions treated. We concluded that LDL apheresis was an efficacious therapy to prevent restenosis after PTCA in patients with hypercholesterolemia.     

Degradation and secretion of insulin in hepatic cirrhosis.

To clarify the mechanism of hyperinsulinism of hepatic cirrhosis, plasma insulin and C-peptide levels before and after oral glucose loads were measured in 34 patients with cirrhosis, 15 patients with chronic hepatitis, and 25 normal subjects. While plasma immunoreactive insulin (IRI) levels during oral glucose tolerance testing (OGTT) were significantly increased in cirrhotics, plasma immunoreactive C-peptide (CPR) levels were elevated slightly. The C-peptide to insulin ratio throughout OGTT was significantly smaller in cirrhotics than in normal subjects (P less than 0.01). A decreased hepatic insulin degradation rate has been suggested to one of the main causes of hyperinsulinism in hepatic cirrhosis. The ratio of the difference between basal and 30-min CPR values and basal and 30-min OGTT blood glucose values [delta CPR: delta BS(30)'] as well as the delta IRI: delta BS(30') ratio was significantly decreased in cirrhotics (P less than 0.01). These results indicate that insulin secretion in response to a glycemic stimulus is reduced in cirrhotics. Both the ratios of the sums of six IRS and CPR values of OGTT (sigma CPR: sigma IRI) and delta CPR: delta BS(30') and sigma CPR: sigma BS(30') were found in inverse relationship with indocyanine green retention rate in cirrhotics.