维生素D_3对报告载体荧光素酶表达的作用

目的：　研究１,２５－二羟维生素Ｄ３ 对结肠癌细胞系Ｃａｃｏ－２ 细胞中报告基因表达的作用,并探讨在报告载体ｐＧＬ２ 序列中存在潜在的抑制性维生素Ｄ应答元件（ＶＤＲＥ）的可能性。方法：　采用磷酸钙沉淀法将报告载体转染入Ｃａｃｏ－２ 细胞。Ｃａｃｏ－２细胞经不同浓度１,２５－二羟维生素Ｄ３ 处理后测定细胞裂解液中表达的荧光素酶活性。结果：　应用ｐＧＬ２ 报告载体时,当用ｐＳＧ５－ＶＤＲ表达载体共转染后,１,２５－二羟维生素Ｄ３显著地抑制Ｃａｃｏ－２ 细胞荧光素酶的表达（Ｐ＜ ０．０５）;而未使用该表达载体共转染则无抑制作用（Ｐ＞ ０．０５）。应用ｐＧＬ３ 报告载体时,不同浓度的１,２５－二羟维生素Ｄ３ 对ｐＬＧ３转染后Ｃａｃｏ－２ 细胞表达的荧光素酶活性均无显著抑制作用（Ｐ＞ ０．０５）,该作用不依赖是否存在有ｐＳＧ５－ＶＤＲ表达载体共转染。结论：１,２５－二羟维生素Ｄ３ 对报告载体ＰＧＬ２ 荧光素酶表达具有抑制作用,而对ｐＧＬ３ 则否;类似人类ＰＴＨ基因中的潜在抑制性ＶＤＲＥ存在于报告载体ｐＧＬ２,在ｐＧＬ３ 中该ＶＤＲＥ业已改变。     

健康寿命年——一个新的测量疾病负担的指标

介绍一种新的测量疾病负担的指标——健康寿命率（ＨｅａＬＹ）。我们用此指标对１９９０～１９９３年北京ＭＯＮＩＣＡ资料进行了重新估算和分析,并将其与几年前ＷＨＯ和世界银行提出的另一个测量疾病负担的指标ＤＡＬＹ进行了比较。     

放射状角膜切开手术中微穿孔对角膜内皮的影响

目的：评价放射状角膜切开术（ＲＫ）中微穿孔对术后１年内角膜内皮的影响。方法：应用角膜内皮镜及角膜内皮分析仪研究４８例ＲＫ术中微穿孔和未穿孔眼的角膜内皮形态学变化,分别在术前及术后１、３、６、１２个月行角膜内皮检查及分析。结果：比较手术前后角膜内皮的数量、平均面积、最大面积和最小面积,穿孔眼及未穿孔眼差异无显著性,但内皮细胞面积两组都有扩大的趋势。结论：ＲＫ术后一年内无论微穿孔还是未穿孔眼的角膜内皮     

Nonsurgical management of extradural hematomas in children

With the advent of computerized tomography (CT), an increasing number of patients with only minimal neurological symptoms and no signs of brain herniation are found to harbor subacute or chronic extradural hematomas (EH's). The authors present the cases of 11 symptomatic but neurologically normal children with medium to large EH's managed by close observation. These EH's were discovered 4 hours to 6 days after injury; three were in the posterior fossa, seven over the frontoparietal convexity, and one in the temporal fossa. These clots were followed by serial CT scans. Nine children recovered without surgery from 4 to 18 days after injury, and all had evidence on CT of spontaneous clot resorption. Of these nine EH's, five clots displayed volume expansion from 5 to 16 days after injury before final resorption occurred. Expansion correlated with persistence or increase in symptoms, whereas resorption correlated with improvement. Two patients showed gradual uncal herniation on Days 6 and 8, respectively, presumably during the "expansile phase" of their clots. Both had emergency craniotomy and recovered without morbidity. It is hypothesized that the resorption dynamics of the subacute or chronic EH are similar to that of the chronic subdural hematoma, with predictable volume changes, and the outcome of each lesion depends on the interplay between the patient's intracranial pressure buffering capacity and the rate of volume change. If subtle signs of brain dysfunction are adopted to signal the failure of conservative treatment and the need for craniotomy, these patients may be safely, and many successfully, managed without surgery. Factors that influence outcome of medical treatment include the size, location, configuration, and the rapidity of accumulation of the clot, the presence of associated intradural lesions, the extracranial decompression of blood through skull diastases, and the age of the patient. These factors, the criteria for patient selection, and the indications for immediate operative intervention are discussed.     

Use of an anal sphincter pressure monitor during operations on the sacral spinal cord and nerve roots

The distinction of sacral roots and conus medullaris from lipoma, fibrous adhesions, and an abnormally thickened filum terminale can be difficult during operations on certain complicated dysraphic lesions. We describe a simple, noninvasive method of monitoring external anal sphincter "squeeze pressure" by means of an elongated, fluid-filled, polyethylene anal balloon connected to a pressure transducer. Cutaneous electrocardiographic (ECG) leads on both hips register the stimulus artifact from a monopolar nerve stimulator. The simultaneous display on the oscilloscope screen of the stimulus artifact and the resultant pressure response form an electromechanical coupling that allows the operator to identify a faulty stimulator probe and to distinguish true stimulus-induced external anal sphincter activity from spontaneous rhythmic contractions of the internal anal sphincter. Unilateral stimulation of the S-2, S-3, and S-4 roots generates tall pressure spikes between 40 and 75 torr in peak amplitudes, whereas S-1 and L-5 stimulation produces a stimulus artifact on the ECG but either no pressure response or a mere "ripple wave" of less than 7 torr. During operations on 11 patients with various dysraphic lesions, the S-2, S-3, and S-4 roots were identified easily and preserved, and the caudal extent of functioning neurons was localized within coni grossly distorted by intramedullary lipoma or chronic tethering. We prefer the anal sphincter pressure monitor to anal sphincter electromyography because of its simplicity, the inexpensive equipment, and its noise-free display that is virtually unaffected by other electronic systems in the operating room.     

蝙蝠葛中的新生物碱——蝙蝠葛新林碱

防已科植物蝙蝠葛(Menispermum daurioum DC.)的根茎,即北豆根,是一种重要的中药,具有清热解毒、消肿止痛等功效。已知含有近二十种生物碱,其中五种属双苄基四氢异喹啉类,即蝙蝠葛碱(dauricine,Ⅰ)、蝙蝠葛诺林碱(daurinoline,Ⅱ)、蝙蝠葛新诺林碱     

Dynamics of drug distribution. I. Role of the second and third curve moments.

Conventionally, the dynamics of distribution in the body is evaluated by the so-called distribution half-life (e.g., t1/2, alpha); but then the mean time of the distribution process is underestimated due to the influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT) and skewness (SDRT) of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), is determined by the mean residence time (MDRT) or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i) the degree of departure of the system from "well-mixed" behavior of instantaneous distribution equilibrium (related to VDRT) and (ii) the mean time until equilibration is achieved (mean equilibration time, MEQT), which additionally depends on SDRT. Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called "distribution phase" in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t1/2,M = t1/2,alpha (V beta/Vss*), where Vss* denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively.     

Subregional topography of capillaries in the dorsal vagal complex of rats: I. Morphometric properties

Cytoarchitectonic and neurochemical studies of the dorsal vagal complex in the caudal medulla oblongata of rats indicate the existence of distinct anatomical and functional compartments within its components. We applied morphometric methods to discern whether capillary networks differed quantitatively between subregions and zones of area postrema, nucleus tractus solitarii (NTS), and dorsal motor nucleus of the vagus nerve (DMN) of rats. Analysis of 11 subdivisions of area postrema identified both "true" (range in luminal diameter of 3-7.5 microns) and sinusoidal (luminal diameter greater than 7.5 microns) capillaries that, together, made the capillary density for most of area postrema 75% greater than that found in NTS and DMN (526/mm2 vs about 300/mm2). The rank order of true capillary density in area postrema along its rostracaudal axis was caudal greater than central greater than rostral, whereas the reverse order was true for sinusoidal capillaries. Dorsal (periventricular) and medial zones of area postrema throughout its rostrocaudal axis tended to have higher values for capillary density, volume, surface area, luminal diameter, and pericapillary space volume than lateral or ventral zones bordering NTS. Within 200 microns of obex, the ventral zone of rostral area postrema was distinct, having a relatively sparse capillary density that may indicate morphological specializations limiting blood-tissue communication in this subregion. There were no quantitative differences in capillary dimensions between DMN and three subnuclei of NTS. These studies add to extant evidence that the dorsal vagal complex is differentiated for specific functions. Area postrema, especially, has topographical diversity in its capillary organization that likely corresponds to complex roles in neuroendocrine, autonomic, and chemosensory mechanisms.     

Hepatic clearance of drugs. II. Experimental evidence for acceptance of the “well-stirred” model over the “parallel tube” model using lidocaine in the perfused rat liverin situ preparation

Theoretical analysis of two models of hepatic drug clearance revealed that one powerful discriminator between them is the effect of changes of hepatic blood flow on either the emergent drug concentration or the availability of a highly extracted compound when operating under linear conditions. Lidocaine (extraction ratio 0.997) was employed in the discriminatory studies. The behavior of this drug under linear conditions (input lidocaine concentrations < 5 mg/ liter) to changes in hepatic blood flow rate (10–16 ml/min per liver) was examined in the perfused rat liver in situpreparation. The steady-state output lidocaine concentration in the blood leaving the liver was predicted better by a well-stirred model than by a parallel tube model. As anticipated, the clearance of a poorly extracted compound, antipyrine (extraction ratio 0.08),was unaltered by changes in hepatic blood flow. These experimental findings, and the data from the literature, point to the acceptance of the well-stirred model, which describes the liver as a well-stirred compartment with the drug in the hepatic venous blood being in equilibrium with that in the liver.Supported in part by National Institutes of Health Grant GM 16496 and the Patent Fund, Graduate Division, University of California, San Francisco.Abstracted in part from a dissertation submitted by K. Sandy Pang to the Graduate Division, University of California, San Francisco, California, in partial fulfillment of the Doctor of Philosophy degree requirements.