Yellow Fever Vaccine. V. Antibody Response in Monkeys Inoculated with Graded Doses of the 17D Vaccine

A dosage equal to or greater than approximately 3.4 Dex (decimal exponent, log(10)) weanling mouse intracerebral 50% lethal dose (LD(50)) was sufficient to elicit a yellow fever antibody response, as determined by the plaque neutralization (PN) test, in better than 90% of vaccinated rhesus monkeys. Lower dosages were progressively less effective in terms of PN titers and the PN and hemagglutination-inhibition serological conversion rates observed. A dose of between 3.4 and 4.2 Dex weanling mouse intracerebral LD(50), or one-tenth to one times the dosage recommended for man, provided an optimal antibody response in monkeys. In rhesus monkeys, in contrast to the findings for man, pre-existing yellow fever antibody did not interfere with the antibody response to yellow fever vaccine. The PN test was felt to be a more sensitive and specific indicator of yellow fever antibody in rhesus monkeys after vaccination than the hemagglutination inhibition or complement fixation tests.     

Helix handedness of Leptospira interrogans as determined by scanning electron microscopy.

Representative serovars and strains of the seven genetic groups of Leptospira interrogans, and two previously studied serovars, were all found to form exclusively right-handed helices as determined by scanning electron microscopy. No change in handedness occurred in cells grown in a minimal medium (Tween-80 albumin) compared to cells grown in a rich medium (rabbit serum). The right-handedness of the organisms was related to the evolution, cell wall structure, and the mechanism of motility of L. interrogans.     

Effect of aeration and sodium on the metabolism of citrate by Klebsiella aerogenes.

Anaerobic growth of Klebsiella aerogenes NCDO 711 (NCTC 418) on citrate was dependent on the presence of Na+ in the medium, and fermentation of citrate was mediated via the fermentation pathway enzymes, citrate lyase and a Na+-dependent oxalacetate decarboxylase. This confirms the previous findings on strain NCTC 418. Growth under aerobic conditions was independent of Na+. The mean generation time for cells grown aerobically on either Na+ or K+ citrate medium was about 60 min, with a molar growth yield of about 40 g (dry weight) of cells per mol of citrate utilized. Citrate was apparently metabolized aerobically in both the Na+ and K+ citrate cells via the citric acid cycle, since cell extracts contained alpha-ketoglutarate dehydrogenase but not the citrate fermentation enzymes. The presence of theother enzymes of the citric acid cycle in K. aerogenes was shown in earlier studies. Under aerated conditions (no detectable oxygen tension in the culture), growth was faster on the Na+ citrate medium (mean generation time, 85 min) than on the K+ citrate medium (mean generation time, 120 min). Both cultures grew slower than under aerobic conditions, presumably because of oxygen limitation. Despite the faster growth rate, the molar growth yield of the aerated Na+ citrate culture was one-half that observed for the aerated K+ citrate culture. Citrate was metabolized via the citric acid cycle in cells grown in the K+ citrate medium under aerated conditions since alpha-ketoglutarate dehydrogenase, but not the fermentation enzymes, was detected in extracts prepared from these cells. Metabolism of citrate in the Na+ citrate medium under aerated conditions occurred via both the fermentation pathway (approximately 75 percent) and the citric acid cycle (about 25 percent), as evidenced by (i) the presence of the fermentation enzymes and alpha-ketoglutarate dehydrogenase in extracts of cells grown under these conditions, (ii) a molar growth yield which was intermediate between that obtained for anaerobic and aerated K+ citrate cultures, and (iii) the excretion of acetate, which also occurred in anaerobic cultures but not in aerated K+ citrate or aerobic cultures.     

Citrate Metabolism in Aerobacter cloacae

Growth of Aerobacter cloacae on citrate either anaerobically or aerobically did not require and was not stimulated by the presence of Na(+) in the medium. Citrate was metabolized anaerobically via the fermentation pathway as evidenced by the (i) presence of oxalacetate decarboxylase, (ii) induction of citrate lyase, and (iii) repression of alpha-ketoglutarate dehydrogenase under anaerobic conditions. Thus, although all the other enzymes of the citric acid cycle were present in anaerobic cells, this pathway was not available for the metabolism of citrate. Citrate was metabolized aerobically via the citric acid cycle, since (i) citrate lyase but not oxalacetate decarboxylase was repressed and (ii) alpha-ketoglutarate dehydrogenase was induced under these conditions. The presence of Na(+) in the medium did not lead to a repression of alpha-ketoglutarate dehydrogenase as in the case of Aerobacter aerogenes. The oxalacetate decarboxylase was a soluble, constitutive enzyme, not activated by Na(+) nor inhibited by avidin. It was slightly inhibited by ethylenediaminetetraacetate but was not stimulated by Mg(2+) or Mn(2+). Thus, this enzyme differed markedly in its properties from the same enzyme found in citrate-grown A. aerogenes.     

Intratumor heterogeneity of biomarker expression in breast carcinomas

Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185^erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA.     

猪源肠球菌的分离及生物特性的初报

本研究从猪粪便中分离了肠球菌两珠,经菌种鉴定两珠菌均为屡肠球菌。其生物特性的研究表明：可耐受15的胆盐和6％NaCI高盐,在pH3．0条件下可存活,对绝大多数抗生素耐药。     

Clinical patterns in asthma based on proximal and distal airway nitric oxide categories

Background

The exhaled nitric oxide (eNO) signal is a marker of inflammation, and can be partitioned into proximal [J''aw_NO (nl/s), maximum airway flux] and distal contributions [CA_NO (ppb), distal airway/alveolar NO concentration]. We hypothesized that J''aw_NO and CA_NO are selectively elevated in asthmatics, permitting identification of four inflammatory categories with distinct clinical features.

Methods

In 200 consecutive children with asthma, and 21 non-asthmatic, non-atopic controls, we measured baseline spirometry, bronchodilator response, asthma control and morbidity, atopic status, use of inhaled corticosteroids, and eNO at multiple flows (50, 100, and 200 ml/s) in a cross-sectional study design. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J''aw_NO and CA_NO.

Results

J''aw_NO was not correlated with CA_NO, and thus asthmatic subjects were grouped into four eNO categories based on upper limit thresholds of non-asthmatics for J''aw_NO (≥ 1.5 nl/s) and CA_NO (≥ 2.3 ppb): Type I (normal J''aw_NO and CA_NO), Type II (elevated J''aw_NO and normal CA_NO), Type III (elevated J''aw_NO and CA_NO) and Type IV (normal J''aw_NO and elevated CA_NO). The rate of inhaled corticosteroid use (lowest in Type III) and atopy (highest in Type II) varied significantly amongst the categories influencing J''aw_NO, but was not related to CA_NO, asthma control or morbidity. All categories demonstrated normal to near-normal baseline spirometry; however, only eNO categories with increased CA_NO (III and IV) had significantly worse asthma control and morbidity when compared to categories I and II.

Conclusions

J''aw_NO and CA_NO reveal inflammatory categories in children with asthma that have distinct clinical features including sensitivity to inhaled corticosteroids and atopy. Only categories with increase CA_NO were related to poor asthma control and morbidity independent of baseline spirometry, bronchodilator response, atopic status, or use of inhaled corticosteroids.     

石耳科(子囊菌亚门)的间断分布和替代现象

本文报道了石耳科的两个亚洲的,也是美洲以外的新记录种,即角石耳与深色石耳。进一步证实了单果石耳在南大西洋的,即南美洲和南部非洲的间断分布。对于上述种类以及本科其它一些种类的间断分布和替代现象进行了分析讨论。     

Induction of tumor promotor-inducible genes in murine 3T3 cell lines and tetradecanoyl phorbol acetate-nonproliferative 3T3 variants can occur through protein kinase C-dependent and -independent pathways.

We isolated a group of genes that are rapidly and transiently induced in 3T3 cells by tetradecanoyl phorbol acetate (TPA). These genes are called TIS genes (for TPA-inducible sequences). Epidermal growth factor (EGF), fibroblast growth factor (FGF), and TPA activated TIS gene expression with similar induction kinetics. TPA pretreatment to deplete protein kinase C activity did not abolish the subsequent induction of TIS gene expression by epidermal growth factor or fibroblast growth factor; both peptide mitogens can activate TIS genes through a protein kinase C-independent pathway(s). We also analyzed TIS gene expression in three TPA-nonproliferative variants (3T3-TNR2, 3T3-TNR9, and A31T6E12A). The results indicate that (i) modulation of a TPA-responsive sodium-potassium-chloride transport system is not necessary for TIS gene induction either by TPA or by other mitogens and (ii) TIS gene induction is not sufficient to guarantee a proliferative response to mitogenic stimulation.