Inhibition of HeLa cell messenger RNA translation by 7-methylguanosine 5'-monophosphate

Translation of HeLa cell RNA containing poly(A) in a wheat germ cell-free system is markedly but incompletely inhibited by 7-methylguanosine 5'-monophosphate (m7G5'p). We have analyzed the translation products synthesized in the presence of different concentrations of m7G5'p and find that translation of all mRNAs is equally inhibited. To demonstrate the specificity of the inhibitor for RNAs with 5'-terminal m7G5' ppp... we show that specific translation products of satellite tobacco necrosis virus RNA, which does not have this 5' terminus, are synthesized in the presence of m7G5' p. Protein synthesis programmed by endogenous mRNA in a HeLa cell-free system is inhibited after a 10-min lag by m7G5' p. Other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position are not inhibitor. We show that translation of all mRNAs is inhibited to a similar extent by m7G5'p in the HeLa cell-free system, by synthesizing 35S-labeled proteins in the presence of different inhibitory concentrations of this nucleotide and analyzing the translation products by electrophoresis and autoradiography. Translation of encephalomyocarditis virus RNA added to the HeLa cell-free system is not inhibited by m7"g5p; this viral RNA does not have this nucleotide at the 5' terminus. This indicates that m7G5'p specifically inhibits translation of mRNAs with the 5' terminus m7G5'ppp... and suggests that initiation of translation of picornavirus RNA may proceed via a mechanism different from that of cellular mRNAs.     

Relationship of passive cigarette-smoking to sudden infant death syndrome

The smoking habits of 56 families who lost babies to the sudden infant death syndrome (SIDS) were compared to those of 86 control families. A higher proportion of SIDS mothers smoked both during pregnancy (61% vs. 42%) and after their babies were born (59% vs. 37%). SIDS mother also smoked a significantly greater number of cigarettes than controls. Exposure to cigarette smoke ("passive smoking") appears to enhance the risk of SIDS for reasons not known.     

The effect of epidural anesthesia on uterine activity and blood pressure

Because of the unresolved controversy regarding the effect of epidural anesthesia upon uterine contractility, it was decided to study its effect on a small number of patients. Intrauterine and intra-arterial continuous pressure, continuous fetal heart rate, and maternal heart rate recordings were obtained from at least 20 minutes before administration of the epidural anesthic until complete dilatation in these patients. Nineteen patients were in spontaneous labor, and 18 had labor stimulated with oxytocin. Plain lidocaine, 1 or 1.5%, was used in 12 patients (30 observations), and lidocaine with epinephrine, 1:200,000 was used in 26 patients (51 observations). Uterine contractions were calculated in Montevideo units for 60 minutes following the epidural anesthetic. The changes, if any, were compared in both groups. There was a significant decrease in uterine activity when epinephrine was added to the anesthetic solution, mainly a lessening of intensity. There were comparable decreases in systolic/diastolic blood pressure in both groups and compensatory tachycardia. In one case, severe hypertension was observed following administration of lidocaine epinephrine. It was concluded that the addition of epinephrine to the anesthetic solution predictably produces diminution of uterine activity, and it does not give "cardiovascular support" to the laboring patient.     

Determination of fibrin and fibrinogen split products by their anticoagulant activity

A new diagnostic method to determine fibrinogen and fibrin splitting products is based on the fact that high-molecular fragments acting as specific inhibitors of fibrin self-assembly compose these products. Fibrinogen and fibrin splitting products are detected and determined quantitatively by prolongation of coagulation time in the test with the standard monomeric fibrin. The number of units of anticoagulating activity in the studied urine are the results of the determinations. Sensitivity of the method if necessary may be increased by adding of a certain amount of the fibrinogen and fibrin splitting products to the test that makes a favourable background for the action of the products. The method is rather sensitive, reliable and simple. It may be used in ordinary clinical laboratories. The method proved to be quite satisfactory when testing renal diseases at the clinic. It is of great significance for early detection of the transplanted kidney rejection. The new method is compared with the known immunological method which consist in determination of the inhibitory effect of the fibrinogen and fibrin splitting products on agglutination of erythrocytes of specific antibodies; the erythrocytes being subjected to "tanning" and "loading" with fibrinogen. A satisfactory correlation is found between the results of two methods.     

Pregnenolone-binding proteins in the rat adrenal cortex

Rat adrenal cortex contains a protein(s) that binds pregnenolone with high affinity. This binding, demonstrated by gel filtration and by a dextran-coated charcoal method, was associated with the cytosol and with fractions solubilized by sonication from the mitochondria and microsomes. The binding of pregnenolone was saturable and was inhibited by mercurials and proteolytic enzymes. Pregnenolone-binding was not influenced by the presence of progesterone, deoxycorticosterone, corticosterone or aldosterone, but was inhibited by steroids with a 3beta-hydroxy-5-ene structure similar to pregnenolone, and by hydroxymethylene steroid and cyanoketone. We suggest that this protein is involved in the intracellular transport and retention of pregnenolone within adrenal cortical cells.     

Production of anti-erythrocyte antibodies by leukemic and nonleukemic B cells in chronic lymphocytic leukemia patients

We have assessed the specificity of antibodies from the leukemic B cells of five patients with both chronic lymphocytic leukemia and autoimmune hemolytic anemia (CLL-AHA). Leukemic cells from one patient displayed surface immunoglobulin with heavy and light chain isotypes identical to that of the patient's anti-red blood cell (RBC) antibodies, and the leukemic cells secreted antibodies in vitro with anti-RBC activity. However, in the remaining patients, the leukemic cells displayed surface immunoglobulin with light chain isotypes different from that of the patient's anti-RBC antibodies and secreted antibodies in vitro with no detectable anti-RBC activity. Thus, there are two distinct classes of CLL-AHA patients, differentiated by the presence or absence of an anti-RBC antibody-producing leukemic B cell clone. The apparent heterogeneity in the source of pathogenic anti-RBC antibodies may impact the treatment response of the two classes of CLL-AHA patients.     

Progress towards a methodology for high throughput 3D reconstruction of soot nanoparticles via electron tomography

The aim of this work is to make progress towards the development of 3D reconstruction as a legitimate alternative to traditional 2D characterization of soot. Time constraints are the greatest opposition to its implementation, as currently reconstruction of a single soot particle takes around 5–6 h to complete. As such, the accuracy and detail gains are currently insufficient to challenge 2D characterization of a representative sample (e.g. 200 particles). This work is a consideration of the optimization of the steps included within the computational reconstruction and manual segmentation of soot particles. Our optimal process reduced the time required by over 70% in comparison to a typical procedure, whilst producing models with no appreciable decrease in quality.     

棉籽壳木聚糖提取液的脱色工艺研究

以伊犁产棉籽壳为原料,比较3种活性炭和3种阴离子交换树脂对棉籽壳木聚糖提取液的脱色效果,确定了最佳脱色条件.结果表明:LY-T-ac型活性炭和D392型阴离子交换树脂对棉籽壳木聚糖液有较好的脱色效果.D392型阴离子交换树脂最佳脱色条件为:脱色温度50℃、pH8.0、脱色时间180 min(150 r/min),在树脂添加量为75 g/L、糖液固形物含量为6％时,脱色率为93.66％.LY-T-ac型活性炭最佳脱色条件为:脱色温度80℃、pH5.0、脱色时间70 min(150 r/min),在活性炭添加量为3g/L、固形物含量为6％时,脱色率为93.51％.     

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.     

Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index

OBJECTIVE: To evaluate the clinical/research utility of the low blood glucose index (LBGI), a measure of the risk of severe hypoglycemia (SH), based on self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS: There were 96 adults with IDDM (mean age 35+/-8 years, duration of diabetes 16+/-10 years, HbA1 8.6+/-1.8%), 43 of whom had a recent history of SH (53 did not), who used memory meters for 135+/-53 SMBG readings over a month, and then for the next 6 months recorded occurrence of SH. The SMBG data were mathematically transformed, and an LBGI was computed for each patient. RESULTS: The two patient groups did not differ with respect to HbA1, insulin units per day, average blood glucose (BG) and BG variability. Patients with history of SH demonstrated a higher LBGI (P < 0.0005) and a trend to be older with longer diabetes duration. Analysis of odds for future SH classified patients into low- (LBGI <2.5), moderate- (LBGI 2.5-5), and high- (LBGI >5) risk groups. Over the following 6 months low-, moderate-, and high-risk patients reported 0.4, 2.3, and 5.2 SH episodes, respectively (P = 0.001). The frequency of future SH was predicted by the LBGI and history of SH (R2 = 40%), while HbA1, age, duration of diabetes, and BG variability were not significant predictors. CONCLUSIONS: LBGI provides an accurate assessment of risk of SH. In the traditional relationship history of SH-to-future SH, LBGI may be the missing link that reflects present risk. Because it is based on SMBG records automatically stored by many reflectance meters, the LBGI is an effective and clinically useful on-line indicator for SH risk.