Methylation of histone H4 by arginine methyltransferase PRMT1 is essential in vivo for many subsequent histone modifications

PRMT1 is a histone methyltransferase that methylates Arg3 on histone H4. When we used siRNA to knock down PRMT1 in an erythroid cell line, it resulted in nearly complete loss of H4 Arg3 methylation across the chicken beta-globin domain, which we use as a model system for studying the relationship of gene activity to histone modification. We observed furthermore a domain-wide loss of histone acetylation on both histones H3 and H4, as well as an increase in H3 Lys9 and Lys27 methylation, both marks associated with inactive chromatin. To determine whether the effect on acetylation was directly related to the loss of H4 Arg3 methylation, we performed an in vitro acetylation reaction on chromatin isolated from PRMT1-depleted cells. We found that nucleosomes purified from these cells, and depleted in methylation at Arg3, are readily acetylated by nuclear extracts from the same cells, if and only if the nucleosomes are incubated with PRMT1 beforehand. Thus, methylation of histones by PRMT1 was sufficient to permit subsequent acetylation. Consistent with earlier reports of experiments in vitro, H4 Arg3 methylation by PRMT1 appears to be essential in vivo for the establishment or maintenance of a wide range of "active" chromatin modifications.     

Long-range temporal correlations in epileptogenic and non-epileptogenic human hippocampus

Epileptogenic human hippocampus generates spontaneous energy fluctuations with a wide range of amplitude and temporal variation, which are often assumed to be entirely random. However, the temporal dynamics of these fluctuations are poorly understood, and the question of whether they exhibit persistent long-range temporal correlations (LRTC) remains unanswered. In this paper we use detrended fluctuation analysis (DFA) to show that the energy fluctuations in human hippocampus show LRTC with power-law scaling, and that these correlations differ between epileptogenic and non-epileptogenic hippocampus. The analysis shows that the energy fluctuations exhibit slower decay of the correlations in the epileptogenic hippocampus compared with the non-epileptogenic hippocampus. The DFA-derived scaling exponents demonstrate that there are LRTC of energy fluctuations in human hippocampus, and that the temporal persistence of energy fluctuations is characterized by a bias for large (small) energy fluctuations to be followed by large (small) energy fluctuations. Furthermore, we find that in the period of time leading up to seizures there is no change in the scaling exponents that characterize the LRTC of energy fluctuations. The fact that the LRTC of energy fluctuations do not change as seizures approach provides evidence that the local neuronal network dynamics do not change in the period before seizures, and that seizures in mesial temporal lobe epilepsy may be triggered by an influence that is external to the hippocampus. The presence of LRTC with power-law scaling does not imply a specific mechanism, but the finding that temporal correlations decay more slowly in epileptogenic hippocampus provides electrophysiologic evidence that the underlying neuronal dynamics are different within the epileptogenic hippocampus compared with contralateral hippocampus. We briefly discuss possible neurobiological mechanisms for LRTC of the energy fluctuations in hippocampus.     

Promising treatments for women with comorbid PTSD and substance use disorders

OBJECTIVE: The authors' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder (PTSD) and substance abuse (seeking safety) with a manualized cognitive behavior therapy that addresses only substance abuse (relapse prevention) and with standard community care for the treatment of comorbid posttraumatic stress disorder (PTSD) and substance use disorder. METHOD: One hundred seven women from an urban, low-income population who had comorbid PTSD and substance use disorder were randomly assigned to receive the two kinds of cognitive behavior therapy or received standard community treatment. Participants were recruited from both community and clinical populations and evaluated with structured clinical instruments. Forty-one women received seeking safety therapy, 34 received relapse prevention therapy, and 32 received standard community care. RESULTS: At the end of 3 months of treatment, participants in both cognitive behavior therapy conditions had significant reductions in substance use, PTSD, and psychiatric symptoms, but community care participants worsened over time. Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group. CONCLUSIONS: Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD, substance use disorder, and other psychiatric symptoms.     

The novel immunosuppressant SDZ-RAD protects rat brain slices from cyclosporine-induced reduction of high-energy phosphates

1. SDZ-RAD, 40-O-(2-hydroxyethyl)-rapamycin, is a novel macrolide immunosuppressant. Because of its synergistic interaction, SDZ-RAD is under clinical investigation as immunosuppressant in combination with cyclosporine after organ transplantation. Neurotoxicity is a critical side-effect of cyclosporine. 2. We studied the effect of SDZ-RAD and its combination with cyclosporine on high-energy phosphates, phosphocreatine (PCr) and nucleoside triphosphates (NTP), in brain slices using 31P-magnetic resonance spectroscopy (MRS). 3. Cyclosporine significantly reduced high-energy phosphates after 2 h in a dose-dependent manner (100 micrograms l-1: 93 +/- 3% of control (NTP), 91 +/- 3% (PCr); 500 micrograms l-1: 84 +/- 2% (NTP), 73 +/- 2 (PCr); 5000 micrograms l-1: 68 +/- 3% (NTP), 55 +/- 5% (PCr); n = 6; P < 0.02). 4. In contrast, after perfusion for 2 h, SDZ-RAD (500 micrograms l-1 and 5000 micrograms l-1) significantly increased high-energy phosphate concentrations in the brain slices (P < 0.02). Even at the lowest concentration, SDZ-RAD protected brain energy metabolism against cyclosporine toxicity: 100 micrograms l-1 SDZ-RAD + 5000 micrograms l-1 cyclosporine: 86 +/- 3% (NTP), 83 +/- 7% (PCr), n = 3, P < 0.03 compared to cyclosporine alone. 5. As evaluated using an algorithm based on Loewe isobolograms, the effects of SDZ-RAD/cyclosporine combinations on brain energy reduction were antagonistic. Both drugs were found in mitochondria using h.p.l.c-MS analysis. 6. We conclude that cyclosporine inhibits mitochondrial high-energy phosphate metabolism, which can be antagonized by SDZ-RAD.     

Utilization of screening mammography: comparison of different physician specialties

Data obtained on 426 consecutive patients referred to a breast center by 122 physicians, including family practitioners, general surgeons, and other specialists, showed that the obstetricians-gynecologists referred the greatest average number of patients per physician, with more than 50% of these referrals for screening mammography. Internists referred fewer patients by nearly a factor of ten, with only one-third of these patients referred for screening mammography. Internists may be the weakest link in the utilization of screening mammography.     

Fluid within preexisting pulmonary air-spaces: a potential pitfall in the CT differentiation of pleural from parenchymal disease

There have been many reports of the ability of CT to distinguish between parenchymal and pleural disease. The purpose of this report is to describe the appearance of seven cases of intraparenchymal fluid-filled air-spaces (bullae or lung cysts) in which the CT findings may resemble those of pleural disease and, thus, cast doubt on the specificity of the established criteria.     

Acute acalculous cholecystitis: sensitivity in detection using technetium-99m iminodiacetic acid cholescintigraphy

Forty-one proved cases of acute acalculous cholecystitis imaged with technetium-99m iminodiacetic acid (IDA) cholescintigraphy were retrospectively analyzed. After the exclusion of one indeterminate scan (showing poor initial hepatic uptake and excretion), the study yielded a 92.5% (37 of 40) sensitivity for the detection of cystic or common bile duct obstruction. Each of the three patients with false-negative scintigrams had other abnormal scintigraphic findings suggestive of biliary tract disease. Of the 20 patients (48.8%) with focal or diffuse gangrenous cholecystitis or perforation, seven (35%) exhibited either free peritoneal spill or increased pericholecystic activity to indicate the presence of advanced disease.     

Factors impacting on shared care working relationships between practice nurses and general practitioners: a literature review

Practice nurses have worked in general practice for many years yet little is known or published in Australia about their work. Recent health care reforms in Australia, particularly the establishment of the Divisions of General Practice and various best-practice innovations linked to the National GP Strategy have seen an increase in the role of practice nurses. Despite this GPs in Australia are cautious about the role of practice nurses. Much of this caution arises from reform in general practice in Britain particularly the establishment of fund-holding for general practice. This article reviews the literature on practice nurses in Britain and Australia within the framework of the health reforms in general practice in both countries.     

犬内皮与平滑肌细胞的短期静态联合培养

目的:为获得组织工程化自体血管,观察体外静态培养条件下犬内皮细胞与平滑肌细胞联合培养组织学及形态学的特征。方法:实验于2004-07/2005-06在首都医科大学宣武医院外科院级实验室完成。①实验材料:雄性杂种犬,3个月龄,体质量8～12kg。②实验方法:贴块法及酶解法对犬内皮细胞及平滑肌细胞进行原代分离培养及扩增,将第Ⅱ代平滑肌细胞以1×109L-1的密度种植于胶原膜上培养13d,再将第Ⅱ代内皮细胞接种于生长平滑肌细胞的胶原膜上2d。③实验评估:行苏木精-伊红染色同时扫描电镜和透射电镜观察平滑肌细胞和内皮细胞在胶原载体上联合培养后的形态。结果:苏木精-伊红染色见平滑肌细胞较均匀的分布于支架材料表面及内部;扫描电镜下,平滑肌细胞可以在胶原载体材料上生长,增殖明显并在短期内形成多层细胞。内皮细胞与平滑肌细胞联合培养2d就可在平滑肌细胞层表面获得连续的单层内皮细胞层。结论:在短期静态培养条件下犬的血管平滑肌细胞和内皮细胞可以在胶原载体材料上形成具有两层细胞结构的组织工程化动脉血管组织片。