Dose evaluation of boron neutron capture synovectomy using the THOR epithermal neutron beam: a feasibility study

Rheumatoid arthritis is one of the most common epidemic diseases in the world. For some patients, the treatment with steroids or nonsteroidal anti-inflammatory drugs is not effective, thus necessitating physical removal of the inflamed synovium. Alternative approaches other than surgery will provide appropriate disease control and improve the patient's quality of life. In this research, we evaluated the feasibility of conducting boron neutron capture synovectomy (BNCS) with the Tsing Hua open-pool reactor (THOR) as a neutron source. Monte Carlo simulations were performed with arthritic joint models and uncertainties were within 5%. The collimator, reflector and boron concentration were optimized to reduce the treatment time and normal tissue doses. For the knee joint, polyethylene with 40%-enriched Li(2)CO(3) was used as the collimator material, and a rear reflector of 15 cm thick graphite and side reflector of 10 cm thick graphite were chosen. The optimized treatment time was 5.4 min for the parallel-opposed irradiation. For the finger joint, polymethyl methacrylate was used as the reflector material. The treatment time can be reduced to 3.1 min, while skin and bone doses can be effectively reduced by approximately 9% compared with treatment using the graphite reflector. We conclude that using THOR as a treatment modality for BNCS could be a feasible alternative in clinical practice.     

Involvement of apoptosis in ovarian follicular atresia and postovulatory regression.

In the ovary, greater than 99% of the follicles present at birth are destined to degenerate during life. In humans, less than 400 of the more than 400,000 follicles found at puberty will eventually ovulate whereas the overwhelming majority of follicles undergo atresia. Although follicular atresia plays a critical role during the recruitment of follicles for ovulation, the exact mechanism of this process is unknown. In chicken and porcine ovaries, atretic follicles can be morphologically distinguished from their healthy counterparts of the same size. Adapting a sensitive 3'-end labeling method for DNA analysis, we identified internucleosomal cleavage of cellular DNA in atretic (but not normal) follicles of both animal species, resembling that found during programmed cell death in embryogenesis, autoimmune T-cell removal and prostate regression. The present findings provide a basis for elucidating the hormonal signals involved in the initiation of follicular atresia during follicle recruitment, reproductive aging and premature ovarian failure.     

Gonadotroph adenomas in men produce biologically active follicle-stimulating hormone

Gonadotroph adenomas may exhibit qualitative and quantitative defects in gonadotropin biosynthesis and secretion. Hypersecretion of immunoreactive FSH dimers by these adenomas occurs frequently; however, it has not been known whether this FSH is biologically active. Using the granulosa cell aromatase bioassay and a highly specific immunoradiometric assay for FSH, we studied the serum bioactivity and bio- to immunoactivity (B/I) ratios of 14 men with FSH-secreting adenomas and compared these values to those of 11 age-matched normal men. In addition, three adenoma patients received TRH (400 micrograms, iv). The mean basal serum FSH level (international units per L), as measured by both bio- and immunoassays, and the FSH B/I ratios were significantly higher (P less than 0.02, by Kolmogorov-Smirnov test) in the adenoma patients than in normal men (mean +/- SEM; adenoma patients: bioactivity, 68.8 +/- 10.4; immunoreactivity, 34.8 +/- 13.7; B/I ratio, 3.4 +/- 0.6; normal men: bioactivity, 5.8 +/- 1.2; immunoreactivity, 6.4 +/- 0.8; B/I ratio, 0.90 +/- 0.1). Both bio- and immunoactive FSH rose after TRH injection, resulting in maintenance of the B/I (mean +/- SEM; pre-TRH: bio-FSH, 63.7 +/- 22.4; immuno-FSH, 28.0 +/- 14.1; B/I ratio, 2.8 +/- 1.2; post-TRH: bio-FSH, 125.6 +/- 42.7; immuno-FSH, 45.8 +/- 21.8; B/I ratio, 3.5 +/- 1.6). When gonadotroph adenoma cells from three separate patients were cultured and their conditioned media (n = 3) studied, relatively large amounts of both bio- and immuno-FSH were detected. Furthermore, the major isoelectric profile of bio-FSH (pH 4.9-3.0) in the conditioned medium from two such adenomas was shown by chromatofocusing to be comparable to that of purified human pituitary FSH (pH 5.2-3.6). We conclude that gonadotroph adenomas in men secrete FSH that is biologically active, both basally and in response to TRH.     

The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques

The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states.     

Associations between Plasma Folate and Vitamin B12, Blood Lead,and Bone Mineral Density among Adults and Elderly Who Received a Health Examination

This study hypothesized that plasma folate and vitamin B₁₂ levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B₁₂, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B₁₂ levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B₁₂ group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).