Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea

Background  

Glioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented.     

Effectiveness of early orthodontic treatment with the Twin-block appliance: a multicenter, randomized, controlled trial. Part 1: Dental and skeletal effects.

This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion. This multicenter trial was carried out in the United Kingdom. A total of 174 children, aged 8 to 10 years old, with Class II Division 1 malocclusion were randomly allocated to receive treatment with a Twin-block appliance or to an untreated, control group. Data were collected at the start of the study and 15 months later. Results showed that early treatment with Twin-block appliances resulted in reduction of overjet, correction of molar relationships, and reduction in severity of malocclusion. Most of this correction was due to dentoalveolar change, but some was due to favorable skeletal change. Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion. The small change in the skeletal relationship might not be considered clinically significant.     

Estrogen receptor beta polymorphisms are associated with bone mass in women and men: the Framingham Study.

ESR2 is expressed in bone cells, yet few studies have tested its variation for association with BMD, an important determinant of osteoporotic fractures. This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men. INTRODUCTION: Osteoporotic fracture risk is highly dependent on bone density, a quantitative multifactorial trait with a substantial genetic component. In contrast to the growing body of evidence that estrogen receptor alpha (ESR1) plays a role in bone metabolism, few studies have examined the estrogen receptor beta (ESR2) gene for association with BMD. An ESR2 CA repeat polymorphism, D14S1026, was associated with BMD in two small studies, each with <200 women. MATERIALS AND METHODS: The objective of this investigation was to assess whether D14S1026 or four other intronic polymorphisms were associated with BMD in 723 men and 795 women (mean age, 60 years) from the offspring cohort of the population-based Framingham Study. BMD was measured at the femur (neck, trochanter, and Ward's area) and the lumbar spine (L(2)-L(4)). RESULTS: In both women and men, there was significant association of D14S1026 genotype with measures of femoral but not spinal BMD. In addition, genotypes of two common single nucleotide polymorphisms, rs1256031 and rs1256059, in strong linkage disequilibrium with one another but not with D14S1026, were associated with measures of femoral BMD in men. The rs1256031 genotypes had up to a 4.0% difference in mean femoral BMD. An inferred rs1256031-D14S1026-rs1256059 haplotype C-23CA-T was significantly associated with reduced femoral BMD in women (p = 0.03, 0.003, and 0.01 for neck, trochanter, and Ward's area, respectively). Haplotype-based BMD differences ranged from 3.0% to 4.3%. CONCLUSIONS: We have observed significant association of common ESR2 variants with measures of femoral BMD in both men and women.     

Potential interference of agents on radioiodide thyroid uptake in the euthyroid rat.

The objective of this research was to investigate the merits of controlled studies with euthyroid rats as a means of determining the influence of dose and time after administration of agents that may interfere with radioiodide uptake in the thyroid. METHODS: Potassium iodide (KI), propylthiouracil (PTU), diatrizoate meglumine, and iohexol were selected to represent interfering agents. Two dose levels per agent were investigated. Doses used were 1 and 2 mg/kg of body weight for KI, 3.5 and 7 mg/kg of body weight for PTU, 1 mL/kg (282 mg I/kg) and 2 mL/kg (564 mg I/kg) of body weight for diatrizoate meglumine, and 1 mL/kg (300 mg I/kg) and 2 mL/kg (600 mg I/kg) of body weight for iohexol. The 24-h radioiodide thyroid uptake was determined after (131)I was given at 1, 8, 15, and 22 d after administration of interfering agents. RESULTS: The percentage radioiodide uptake value for the thyroid decreased significantly compared with controls for all agents and both doses on day 1 but returned to control levels by day 22 for all agents and both doses The time to return to normal varied between agents and doses. CONCLUSION: We conclude that the interfering agent, the dose given, and the length of time after administration influence the potential for an agent to affect radioiodide uptake in the thyroid. Further studies with the rat, preferably hyperthyroid, would be beneficial in generating data to reduce confusing contradictory information on the length and severity of interference of agents in radioiodide thyroid studies.     

Changes in bladder function following a surgical alteration in outflow resistance

The changes in bladder function occurring after a surgical alteration in bladder outflow resistance were studied in 20 males undergoing transurethral prostatectomy (TURP) and in 20 females undergoing an endoscopic bladder neck suspension (EBNS). Serial cystometrograms (CMG) were performed before operation, and on alternate days after spontaneous micturition was re-established, for 5 days in the males and for 21 days in the females. CMGs were repeated at 3 months and 1 year after operation. After TURP voiding pressures (P_det) fell rapidly from a mean of 118 cm H₂O before operation to 57 cm H₂O at 5 days, with an increase in flow rate during this time from 10.5 ml/s to 24 ml/s. Detrusor instability that had been present in 14 patients resolved within 2 days in 12. There was no further significant urodynamic change over the 1-year study period. After EBNS, there was an early rise in voiding pressure (P_det rose from 26 cm H₂O before operation to 42 cm H₂O at 3 days). This continued to increase up to 21 days particularly in those patients with initial large residuals. Three patients developed detrusor instability. Flow rates were greatly reduced at first (27 ml/s before operation and 13 ml/s at 3 days), and gradually increased in line with voiding pressures, yet were still diminished 1 year after operation. The urodynamic changes following a reduction in bladder outflow resistance by TURP are immediate and sustained and unlikely to be the result of structural changes within the bladder wall. EBNS produces an increase in outflow resistance and it can be several weeks before balanced voiding is achieved, with significantly increased detrusor pressures needed to achieve complete bladder emptying at a reduced flow rate.