A NEW VASOCONSTRICTOR—A Preliminary Report

Otrivin,® a compound of the hydrochloride salt of phenyl-aminomethylimidazoline, was administered to 74 patients for varying periods as a nasal vasoconstrictor. Seventy-three had relief of nasal congestion for from five to six hours—longer periods than had been obtained with other vasoconstrictors they had used. No pressor effect was noted.     

VITAMIN A AND UROLITHIASIS—A Review

The early observations of Osborne, Mendel, and Ferry, and later of Higgins, showed that the incidence of urolithiasis was high in rats fed on diets deficient in fat soluble vitamins. Subsequently, the results of dark adaptation studies were interpreted as showing a relationship between vitamin A deficiency and calculous disease. However, a review of the literature including more recent data discloses that there is no evidence either clinical or experimental to support the claim that vitamin A deficiency is an etiologic factor in calculous disease in man in the United States.     

Adenosine A₂A and A₂B receptors are both required for adenosine A₁ receptor-mediated cardioprotection

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A(2A) and/or A(2B) receptors modulate adenosine A(1) receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A(2A) knockout (KO), and A(2B)KO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A(1) receptor agonist N(6)-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A(2A) receptor agonist CGS-21680 (200 nM) and the A(2B) agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A(2A) or A(2B) receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A(2A) and A(2B) receptors are required for adenosine A(1) receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.     

Synthesis of 27-Oxo, 27-Hydroxymilbemycins A3 and A4 and Novel 27-Alkoxymilbemycins A3 and A4 from Milbemycins A3 and A4 and…

27-Oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ were identified as metabolites in soil metabolism studies of milbemycins A₃ and A₄. Chemical derivation methods were developed to synthesize 27-oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ from milbemycins A₃ and A₄. In addition, 27-alkoxymilbemycin derivatives were also synthesized from the same precursors. Some of the synthesized compounds displayed satisfactory acaricidal activity against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae), but did not have superior activity to corresponding milbemycins A₃ and A₄.     

赤霉素A4,A7的研究进展

赤霉素Ａ＿４、Ａ＿７的研究进展颜方贵,秦杰,何增国,李季伦（北京农业大学生物学院,北京１０００９４）赤霉素Ａ＿３（ＧＡ＿３）是目前应用最广的植物生长激素之一。随着研究的深入,对该族的其它同系物,特别是ＧＡ＿４、ＧＡ＿７越来越受到重视,这是由于ＧＡ＿４...     

DOES A NORMAL FOETUS REALLY HAVE A FUTURE OF VALUE? A REPLY TO MARQUIS

The traditional approach to the abortion debate revolves around numerous issues, such as whether the foetus is a person, whether the foetus has rights, and more. Don Marquis suggests that this traditional approach leads to a standoff and that the abortion debate 'requires a different strategy.' Hence his 'future of value' strategy, which is summarized as follows: (1) A normal foetus has a future of value. (2) Depriving a normal foetus of a future of value imposes a misfortune on it. (3) Imposing a misfortune on a normal foetus is prima facie wrong. (4) Therefore, depriving a normal foetus of a future of value is prima facie wrong. (5) Killing a normal foetus deprives it of a future value. (6) Therefore, killing a normal foetus is prima facie wrong. In this paper, I argue that Marquis's strategy is not different since it involves the concept of person--a concept deeply rooted in the traditional approach. Specifically, I argue that futures are valuable insofar as they are not only dominated by goods of consciousness, but are experienced by psychologically continuous persons. Moreover, I argue that his strategy is not sound since premise (1) is false. Specifically, I argue that a normal foetus, at least during the first trimester, is not a person. Thus, during that stage of development it is not capable of experiencing its future as a psychologically continuous person and, hence, it does not have a future of value.     

赤霉素A4、A7的发酵研究

初选藤仓赤霉菌(Gibberella fujikuroi)农大17菌株为赤霉素A_4、A_7(GA_4、GA_7)的生产菌,该菌株GA_(4+7)的积累量,除与营养条件有关外,温度和pH是极为重要的因子,随着发酵温度从28℃上升至32℃,GA_(4+7)的产量由21μg/ml增至81μg/ml,GA_3由702μg/ml降至328μg/ml。pH回调至中性,GA_(4+7)的产量由75μg/ml增至180μg/ml,GA_3由322μg/ml降至211μg/ml。此外,设法延长发酵周期也是增加GA_(4+7)的一个因素。综合上述条件,即发酵过程中,发酵液的pH由48h前的4回调并维持在6.7左右,温度由28℃上调并控制在32℃,摇瓶培养12天,GA_(4+7)的产量达890μg/ml,20—600L发酵罐发酵240h,GA_(4+7)产量达680μg/ml左右。GA_(4+7)浓度的测定亦作了简化处理,发酵液不经提取,可直接用硅胶板G薄层层析(TLC)后进行荧光比色,产品测定宜采用高效液相色谱法(HPLC)。按照上述条件培养的农大17菌株,产生GA_3、GA_7和GA_4的比例为23.131:16.105:31.258,GA_4高于有关报道。     

葡萄球菌A蛋白

金黄色葡萄球菌的细胞壁含有三种主要成份:核糖醇磷壁酸、粘肽及A蛋白(SPA)。因A蛋白具有能与免疫球蛋白的Fc段相结合的特性,已广泛应用于细菌、病毒等病原诊断、分型(如肺炎双球菌和链球菌的分型)、免疫球蛋白提取和测定、细胞的分离、分析淋巴细胞表面结构及免疫理论研究等方面,并具有广泛的应用前途。     

A.A.Khan教授将来华讲学

美国康乃尔大学种子生理学家A.A.Khan教授,将于今年十月中旬来华,到广州及杭州访问,并在广州举办讲习班,做以下五方面的报告:①应用种子预措施改善幼苗生长与产     

A monoclonal antibody against synthetic Aβ dimer assemblies neutralizes brain-derived synaptic plasticity-disrupting Aβ

Diverse lines of evidence indicate that pre-fibrillar, diffusible assemblies of the amyloid β-protein (Aβ) play an important role in Alzheimer's disease pathogenesis. Although the precise molecular identity of these soluble toxins remains unsettled, recent experiments suggest that sodium dodecyl sulfate (SDS)-stable Aβ dimers may be the basic building blocks of Alzheimer's disease-associated synaptotoxic assemblies and as such present an attractive target for therapeutic intervention. In the absence of sufficient amounts of highly pure cerebral Aβ dimers, we have used synthetic disulfide cross-linked dimers (free of Aβ monomer or fibrils) to generate conformation-specific monoclonal antibodies. These dimers aggregate to form kinetically trapped protofibrils, but do not readily form fibrils. We identified two antibodies, 3C6 and 4B5, which preferentially bind assemblies formed from covalent Aβ dimers, but do not bind to Aβ monomer, amyloid precursor protein, or aggregates formed by other amyloidogenic proteins. Monoclonal antibody 3C6, but not an IgM isotype-matched control antibody, ameliorated the plasticity-disrupting effects of Aβ extracted from the aqueous phase of Alzheimer's disease brain, thus suggesting that 3C6 targets pathogenically relevant Aβ assemblies. These data prove the usefulness of covalent dimers and their assemblies as immunogens and recommend further investigation of the therapeutic and diagnostic utility of monoclonal antibodies raised to such assemblies.     

Aβ40(L17A/F19A) mutant diminishes the aggregation and neurotoxicity of Aβ40

Aggregated β-amyloid peptides (Aβ) are neurotoxic and responsible for neuronal death both in vitro and in vivo. From the structural point of view, Aβ self-aggregation involves a conformational change in the peptide. Here, we investigated the relationship between conformational changes and amino acid residues of Aβ₄₀. Urea unfolding in combination with NMR spectroscopy was applied to probe the stabilization of Aβ₄₀ conformation. L17 and F19 residues were found more sensitive to environmental changes than the other residues. Replacement of these two residues with alanine could stabilize the conformation of Aβ₄₀. Further analysis indicated that the Aβ₄₀(L17A/F19A) mutant could diminish the aggregation and reduce the neurotoxicity. These results suggest that L17 and F19 are the critical residues responsible for conformational changes which may trigger neurotoxic cascade of Aβ₄₀.     

Immunoglobulin A: A next generation of therapeutic antibodies?

Although immunoglobulin (Ig) A is commonly recognized as the most prevalent antibody subclass at mucosal sites with an important role in mucosal defense, its potential as a therapeutic monoclonal antibody is less well known. However, IgA has multifaceted anti-, non- and pro-inflammatory functions that can be exploited for different immunotherapeutical strategies, which will be the focus of this review.Key words: IgA, SIgA, dIgA, CD89, FcαRI, therapy, pro-inflammatory, mucosal defence, tumor, ITAM     

Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

Beta-amyloid (Aβ) aggregates have a pivotal role in pathological processing of Alzheimer’s disease (AD). The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.     

A New Tandem Repeat in Bovine Fibrinogen Aα Gene

In this study, we describe intraspecies variation in the αC connector region of the bovine fibrinogen Aα gene. Sequencing and genotyping of six bovine breeds revealed 7 to 10 tandem repeats in the αC connector region. In addition, we observed length differences between B. indicus and B. taurus, with the B. indicus having longer fibrinogen αC connectors (10-repeat alleles) than B. taurus (7- and 9-repeats). The difference in tandem repeats may be related to the function of blood coagulation system.