Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.     

彻罗基族印地安儿童及青少年的体重指数和高密度脂蛋白

美国原著民易于出现胰岛素抵抗及相关的心血管病风险。因此，笔者对彻罗基族儿童和青少年的体重指数（BMI）是否与HDL—C（HDL胆固醇）、HDL微粒Lp（脂蛋白）A-Ⅰ和LpA-Ⅰ：A-Ⅰ相关进行了研究。在三个性别特异的年龄段（5～9岁，10～14岁和15～19岁）内按照BMIZ值的四分位值对研究对象进行分组，研究其肥胖和年龄相关的脂蛋白和HOMA—IR（HOMA模型胰岛素抵抗指数）值的趋势。在两个性别的三个年龄组中，HDL—C随着BMIZ值的四分位值的增加而降低。HDL-C、LpA-Ⅰ和LpA-Ⅰ：A-Ⅱ在男孩中随着年龄增加而降低，在女孩中则没有观察到该变化。在两个性别的三个年龄组中，Log HOMA-IR随着BMIZ值的四分位值的增加而增加。线性回归模型显示BMIZ值、甘油三酯和年龄与HDL—C相关，     

Cerebrospinal fluidCHOLINESTERASES—MARKERS for loss ofcholinergic basal forebrain neurons?

The present study was conducted to test the hypothesis that cholinergic basalforebrain neurons are a major source of cerebrospinal fluid (CSF) cholinesterases. To address thisquestion enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inboth CSF and parietal cortex were assayed following selective lesion of basal forebrain cholinergicneurons by a single intracerebroventricular application of the cholinergic immunotoxin192IgG-saporin. Cholinergic immunolesions led to a dramatic decrease in total AChE activity inparietal cortex, which was due to the specific loss of the G4 molecular form while the activity ofthe G1 form was increased as compared to nonlesioned animals. In contrast, the total enzymeactivity of BChE and its molecular forms were not affected by cholinergic lesion in both parietalcortex and CSF. The data suggest, that cholinergic basal forebrain neurons are seemingly not amajor source of cholinesterases in the CSF, and do not provide any evidence for using CSFcholinesterases as a diagnostic marker of basal forebrain cholinergic cell loss in humans.     

Principal neuron spiking: neither necessary nor sufficient for cerebral blood flow in rat cerebellum

Neuronal activity, cerebral blood flow, and metabolic responses are all strongly coupled, although the mechanisms behind the coupling remain unclear. One of the key questions is whether or not increases in spiking activity in the stimulated neurons are sufficient to drive the activity-dependent rises in cerebral blood flow (CBF) that form the basis of the signals used in functional neuroimaging such as the blood oxygen level-dependent (BOLD) signal. To this end the present study examined the effect of enhanced spike activity per se on CBF in rat cerebellar cortex under conditions of disinhibition, achieved by blocking GABA_A receptors using either bicuculline or picrotoxin. Purkinje cell spiking activity and local field potentials were recorded by glass microelectrodes, and laser Doppler flowmetry was used to monitor CBF. Disinhibition increased Purkinje cell spiking rate to 200–300% of control without incurring any increase in basal CBF. This demonstrates that increased spike activity per se is not sufficient to affect basal CBF. The neurovascular coupling between excitatory synaptic activity and CBF responses evoked by inferior olive (climbing fibre) stimulation was preserved during disinhibition. Thus, the unchanged basal CBF in the presence of the dramatic rise in Purkinje cell spiking rate was not explained by impaired synaptic activity–CBF coupling. On the basis of our previous and the present studies, we conclude that increased spiking activity of principal neurons is neither sufficient nor necessary to elicit CBF responses and in turn BOLD signals, and that activation-dependent vascular signals reflect excitatory synaptic activity.     

Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion

During the process of malignant transformation, nascent melanoma cells escape keratinocyte control through down-regulation of E-cadherin and instead communicate among themselves and with fibroblasts via N-cadherin-based cell-cell contacts. The zonula occludens (ZO) protein-1 is a membrane-associated component of both the tight and adherens junctions found at sites of cell-cell contact. In most cancers, levels of ZO-1 are typically down-regulated, leading to increased motility. Here we report the novel observation that ZO-1 expression is up-regulated in melanoma cells and is located at adherens junctions between melanoma cells and fibroblasts. Immunofluorescence and co-immunoprecipitation studies showed co-localization of ZO-1 with N-cadherin. Down-regulation of ZO-1 in melanoma cells through RNA interference produced marked changes in cell morphology--leading to a less-dendritic, more rounded phenotype. Consistent with a role in N-cadherin-based adhesion, RNAi-treated melanoma cells were less adherent and invasive when grown in a collagen gel. These data provide the first evidence that increased ZO-1 expression in melanoma contributes to the oncogenic behavior of this tumor and further illustrate that protein products of genes, such as ZO-1, can function in either a pro- or anti-oncogenic manner when expressed in different cellular contexts.     

Effects of delta-9-tetrahydrocannabinol on cultured HeLa cell growth and development

Monolayer cultures of HeLa cells were used to monitor the effects of non-lethal concentrations of delta-9-tetrahydrocannabinol (delta-9-THC) on the pool sizes of the acid-soluble and acid-insoluble DNA moieties and cytoplasmic RNA pool sizes. The DNA fractions were separated using acid precipitation and low speed centrifugation, while the RNA was examined through the use of sucrose gradients and high speed ultracentrifugation. The ratio of acid-insoluble to acid-soluble DNA per cell in untreated HeLa cells is 16:1, which did not change appreciably following delta-9-THC treatment. However, cell division was retarded as much as 25% in the 24 hours treatment period indicating that nucleic acid synthesis, while not inhibited, is depressed by delta-9-THC. This is not related to cell death as indicated by cell viability (> 95%). At both 1.0 x 10(-5)M and 3.2 x 10(-7)M, delta-9-THC caused a marked change in the free ribosomal RNA (an increase with 3.2 x 10(-7)M and a decrease with the 10(-5)M), total ribosomal RNA (a decrease with both observed delta-9-THC concentrations) and non-sedimental RNA (an increase with both observed delta-9-THC concentrations).     

Chemically-induced histone modification as a predictor of carcinogenicity

The interaction between carcinogens and DNA is believed to initiate neoplastic transformation, but evidence suggests that epigenetic mechanisms may also be of importance. Because the histone proteins have important roles in chromatin structure and cellular function, they provide a reasonably well understood epigenetically-based system for the detection of carcinogens. In this study, human foreskin fibroblastic cells were exposed to one of several mutagens and/or carcinogens for 3, 12, or 24 h to determine if induced histone modification may be a means of predicting chemical carcinogenicity.Butyric acid (5 mM), known to result in acetylation of histones H3 and H4, and 12-O-tetradecanoylphorbol-13-acetate (3 M), known to result in phosphorylated histone H1, were tested initially. Electrophoresis of the histone fractions was capable of resolving multiple forms of histones H1, H3, and H4.Propane sultone (0.1 mM) induced a broadening of the H2A and H2B bands after a 24 h exposure and carbon tetrachloride (1 mM) induced the formation of new histone forms in the H1 fraction after 24 h and in the H3 fraction after 3 h. Experimental variability limited the statistically significant modifications to carbon tetrachloride and propane sultone, two known carcinogens, where new forms of modified histone were detected. Therefore, the histone modification assay, with further experimentation, may be an alternate method of detecting carcinogens, especially when conventional genotoxic tests prove unreliable.     

The role of the radiology nurse

The radiology nurse's role requires a high level of knowledge, expertise and independence because the department provides services to a wide variety of patients with diverse needs and about whom information may be limited. Radiology nurses routinely start or check peripheral i.v.s, assess infusaports, administer medications, monitor vital signs, suction patients, insert foleys and help patients with their personal needs. The nurse also informs the technologist or radiologist of any unusual patient needs and performs specialized nursing duties, such as administering i.v. sedation or analgesia during special procedures and closely monitoring patients with cardiac/pulse oximeters. Radiology departments call on nurses to care for patients transported from intensive care, patients in emergency situations and pediatric patients and others needing sedation. Teaching is another duty radiology nurses assume, instructing patients and their families, students, technologists, other nurses, radiologists and physicians about patient care. They also teach the radiology staff new nursing policies and national standards as such changes occur. Radiology nurses devote a lot of time to quality improvement and infection control programs: collecting data, keeping records and reporting results. Because radiology nursing is relatively new, the nurse may be called upon to help write patient care policies, design flowsheets or patient instruction sheets and develop protocols or care plans. Radiology nurses utilize skills employed in many other nursing specialties and incorporate them in the radiology setting. They must provide quality nursing care to a large, transient group of patients of all ages, be a spokesperson for patient care and a teacher to other radiology staff members on patient care issues.