4-酰胺基-4-脱氧-4′-去甲表鬼臼毒素衍生物的合成和抗肿瘤活性

4′-去甲表鬼臼毒素与叠氮酸在三氟化硼乙醚存在下缩合,并经还原得4-氨基-4-脱氧-4′-去甲表鬼臼毒素。该中间体与酸或酸酐反应得相应酰胺化合物24个。经体外筛选,多数化合物抑制L₁₂₁₀和KB细胞活性相当或超过依托泊甙。与相应的醚、酯、胺等类型相比,这一类化合物活性最强。     

Autostimulation of growth by human myelogenous leukemia cells (HL-60)

We have studied the effects of medium conditioned by the human progranulocytic leukemia cell line, HL-60, on the subsequent growth of new inocula of HL-60 cells. When HL-60 cells were cultured at high cell density, optimal growth rate occurred in liquid suspension and confluent colony growth was observed in viscous medium without the addition of conditioned medium. However, when cells were cultured at lower cell density, growth rate was reduced and colony growth was nil unless conditioned medium from HL-60 culture was added. All HL-60 populations studied, including the earliest available passage, 9, both elaborated and responded to HL-60 CM. HL-60 CM did not stimulate normal human or mouse granulocyte-monocyte colony-forming cell (CFU-GM) growth. Conditioned media from other human cell lines varied in the ability to stimulate HL-60 cell and CFU-GM proliferation. Some, such as GCT CM, stimulated both HL-60 cells and normal CFU-GM, whereas others, like HL-60 CM, stimulated only HL-60 growth. The majority of cell line CMs tested did not stimulate either HL-60 or CFU-GM. Chromatography of HL-60 CM on Ultrogel AcA54 showed a single peak of HL-60 stimulating activity of apparent molecular weight 13,000. The ability of HL-60 cells to elaborate this activity provides a possible explanation for their proliferation at higher cell densities. Autostimulation may prove to be important in the high growth potential of other cell populations that undergo unrepressed proliferation.     

Simulation and its role in medical education

Medical education is increasingly laying emphasis on a curriculum based on cognitive, psychomotor, and affective domains of learning which were originally proposed nearly 50 years ago. These reforms are framed around best standards of care, error management and patient safety, patient autonomy, and resource allocation. There is a worldwide shift in the method of medical education towards experiential (‘hands-on’) medical learning; however, applying this concept to real patients is less acceptable to society and is subject to legal and ethical issues.     

Mild idiopathic lateral cerebral ventricular dilatation in utero: sonographic evaluation

The authors prospectively studied 20 fetuses with mild dilatation of the lateral cerebral ventricles but no other detectable central nervous system abnormality. One case (5%) occurred in a diabetic pregnancy, and three (15%) involved twin pregnancies. Fifteen (75%) fetuses were male, and one (5%) had trisomy 21. Postnatal follow-up at 15-31 months showed a normal outcome in eight cases (40%), an uncertain prognosis in four cases (20%), and death in eight cases (40%). Serial antenatal sonograms were obtained in 17 cases. Among the eight cases with a normal outcome, seven demonstrated no additional sonographic abnormalities and six showed resolution of the ventricular dilatation antenatally. Conversely, all 12 fetuses with demise or an uncertain prognosis demonstrated additional sonographic abnormalities, and six showed stable or progressive ventricular dilatation on follow-up sonograms. Since mild idiopathic lateral ventricular dilatation has a widely variable prognosis, antenatal detection of this finding warrants search for additional findings and follow-up sonography.     

Subthreshold Oscillations Induced By Spinal Nerve Injury In Dissociated Muscle And Cutaneous Afferents Of Mouse DRG

Whole cell patch-clamp recordings were obtained from dissociated mouse lumbar dorsal root ganglion (DRG) neurons. Recordings were made from control neurons and neurons axotomized by transection of the corresponding spinal nerve 1-2 days prior to dissociation. Medium to large muscle and cutaneous afferent neurons were identified by retrograde transport of True Blue or Fluoro-Gold injected into the corresponding peripheral tissue. Action potentials were classified as non-inflected spikes (A(0)) and inflected spikes (A(inf)). High-frequency, low-amplitude subthreshold membrane potential oscillations were observed in 8% of control A(0) neurons, but their incidence increased to 31% in the nerve injury group. Fifty percent of axotomized muscle afferent A(0) cells displayed oscillations, while 26% of axotomized cutaneous afferents exhibited oscillations. Lower-frequency oscillations were also observed in a small fraction (4%) of A(inf) neurons on strong depolarization. Their numbers were increased after the nerve injury, but the difference was not statistically significant. The oscillations often triggered burst firing in distinct patterns of action potential activity. These results indicate that injury-induced membrane oscillations of DRG neurons, previously observed in whole DRG of rats, are present in dissociated DRG neurons of the adult mouse. Moreover, these observations indicate that both muscle and cutaneous afferents in the A(beta) size range give rise to injury-induced membrane oscillations, with muscle afferents being more prone to develop oscillations.     

Antibody to Hepatitis B Surface Antigen in Vaccinated Health Care Workers

Background

Health care workers (HCWs) in Armed Forces are immunised against Hepatitis B virus (HBV), however they are not subjected to anti-HBs (antibody to Hepatitis B surface antigen) assessment after primary vaccination. The present study was undertaken to determine the protection offered by HBV vaccine in HCW.

Methods

Cross-sectional study was carried out at tertiary care hospital. A total 146 HBV vaccine compliant HCW were evaluated for quantitative anti-HBs by enzyme immune assay.

Result

129 (88.4%) subjects had protective levels of anti-HBs. Higher age at vaccination was an important risk factor in low vaccine response. Decline in anti-HBs with time was evident. Anti-HBs levels were more than 10mIU/ml in subjects even after 11 years of primary vaccination. There was no difference in protection in booster and non booster groups.

Conclusion

Age is the most important factor in HBV vaccine response. Booster dose of HBV vaccine is not necessary in healthy HCW for atleast ten years after primary vaccination. The study recommends early primary vaccination of HCW and ‘initial’ anti-HBs assay for confirmation of vaccine response.Key Words: Anti-Hepatitis B surface antigen, Health care workers, Hepatitis B virus vaccine