基因测序确认一例新β地中海贫血基因突变CD112（T→A）

目的 报道1例中国人少见的β地中海贫血基因突变CD112（T→A）／N。方法 根据血常规平均红细胞体积（MCV）和平均血红蛋白含量（MCH）以及血红蛋白电泳的HbF和HbA2对婚检和产检患者筛查地中海贫血，对可疑β地中海贫血患者采用基因扩增反向点杂交法检测常见17个位点突变。对于未发现突变者采用基因测序。结果 患者携带一种中国人少见的B地贫基因突变CD112（T→A）。结论 β地贫基因CD112（T→A）突变的报道丰富了中国人β地贫突变谱。对于指导婚检、产检、遗传咨询具有重要价值。     

Airway responses to antigen challenge in allergic rhinitis and allergic asthma

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC), and specific airway conductance (SGaw) were determined before and during bronchial provocation with ragweed extract in 27 subjects with ragweed hypersensitivity and a history of either bronchial asthma (16 subjects) or allergic rhinitis (11 subjects). Mean baseline SGaw was significantly lower while mean volume of isoflow (Visov) and FrC were significantly higher in subjects with bronchial asthma. During antigen challenge, 10 of 16 subjects with bronchial asthma (63%) and five of 11 subjects with allergic rhinitis (45%) showed a greater than 35% decrease in SGaw ("reactors"): mean relative decreases in SGaw from baseline were 46% and 53%, respectively. The remaining subjects showed a less than 35% decrease in SGaw ("nonreactors") with mean relative decreases of 9% (allergic asthma) and 6% (allergic rhinitis). Mean Visov increased in all subjects with bronchial asthma and in eight of 11 subjects with allergic rhinitis. A significant increase in FRC (6%) was seen only in the "reactors" with bronchial asthma. Following antigen challenge, the beta adrenergic agonist, isoetharine, increased SGaw and decreased Visov. We conclude that in asymptomatic subjects with ragweed hypersensitivity, (1) central and peripheral airway function is more abnormal in subjects with bronchial asthma than in subjects with allergic rhinitis, (2) subjects of both groups show quantitatively and qualitatively comparable airway responses during antigen challenge with a decrease in SGaw or an increase in Visov, possibly representing increase in central and/or peripheral airflow resistance, respectively, (3) Visov may be a more sensitive indicator of airway response to antigen challenge than SGaw, and (4) the bronchodilator effects of a beta adrenergic agonist on antigen-induced bronchospasm are similar in both groups.     

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Δ⁹-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 μg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.     

Virion-bound ICAM-1 and activated LFA-1: a combination of factors conferring resistance to neutralization by sera from human immunodeficiency virus type 1-infected individuals independently of the disease status and phase

The role of the supplementary interaction between virion-bound host ICAM-1 and LFA-1 on target cells in sensitivity to neutralization of human immunodeficiency virus type 1 (HIV-1) is poorly studied. Serum samples from four long-term nonprogressors (LTNPs) and sequential sera from one progressor were used to assess neutralization sensitivity of isogenic ICAM-1-negative and ICAM-1-bearing HIV-1(NL4-3), a prototype of T-cell-line-adapted viruses. We found that virus neutralization sensitivity to the studied sera is not modified by the additional interaction between virally embedded ICAM-1 and LFA-1 under an inactive state. However, expression on the target cell surface of an activated LFA-1 form renders ICAM-1-bearing virus particles, but not viruses devoid of ICAM-1, more refractory to neutralization by sera from three out of four LTNPs and all sequential sera from the person who has experienced a progression of the HIV-1-associated disease. Although no conclusive correlation could be drawn between virus susceptibility to neutralization and the disease status or stages of HIV-1 infection, these findings demonstrate that other nonspecific virus-cell interactions mediated by virion-anchored host proteins and their normal cognate ligands on target cells represent factors that can affect the mechanism of HIV-1 neutralization.     

Développement d’un hydrogel autodurcissant in vivo, en perspective d’un usage biomédicalA new self-hardening gel in prospect of biomedical use

Since 1995, an injectable bone substitute is developed in our laboratory, it is based on a mix of an hydrogel (hydroxypropyl methylcellulose at 3%: cellulose ether) and biphasic calcium phosphate granules (MBCP^® : 60% hydroxyapatite, 40% β-tri calcium phosphate). This first generation of injectable bone substitute is a non-self-hardening past, nevertheless it owns a great osteoconductor potential. But it shows a tendency to the discharge by its initial composition, and involved limited clinical applications. An evolution of this product is presented in this article: the modification is generated by a new self-hardening hydrogel. This hydrogel is a cellulose ether grafted by silane and diluted in an aqueous solution at basic pH. Also it will be presented the general synthesis of this cellulose derivate, the dissolution condition and the self hardening principle in function of the pH and the temperature. As to conclude by preliminary tests, the biocompatibility in vivo and in vitro of the self-hardening hydrogel mixed with biphasic calcium phosphate granules will be studied.     

A clinical trial of adjunctive oestrogen treatment in women with schizophrenia

Summary A double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 μg transdermal estradiol or b) 100 μg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 μg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 μg estradiol or placebo groups. The addition of 100 μg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia. Accepted June 2002, Published online September 16, 2002 Correspondence: Prof. Jayashri Kulkarni, Alfred Psychiatry Research Centre, Alfred Hospital, Commercial Road, Prahran. Vic. 3181, Australia; e-mail: jayashri.kulkarni@med.monash.edu.au     

Polysialic acid, a unique glycan that is developmentally regulated by two polysialyltransferases, PST and STX, in the central nervous system: From biosynthesis to function

Polysialic acid is a developmentally regulated carbohydrate composed of a linear homopolymer of a-2,a-linked sialic acid residues. This unique glycan is mainly attached to the neural cell adhesion molecule (N-CAM) and implicated in many morphogenic events of the neural cells by modulating the adhesive property of N-CAM. Recently, the cDNA that encodes polysialyltransferase, which is responsible for the polysialylation of N-CAM, was successfully cloned from three mammalian species. This review focuses on the molecular cloning of human polysialyltransferase, designated PST. it then describes the number of enzymes actually required for the polysialylation of N-CAM using an in vitro polysialyltransferase assay. Comparisons between PST and another polysialyltransferase, sialyltransferase X (STX), are made and it Is demonstrated that both enzymes can independently form polysiatic acid In vitro , but that during neural development they coordinately but distinctly synthesize polysialic acid on N-CAM. The role of polysialic acid in the central nervous system is also discussed. Finally, evidence that the two polysialyltransferases, PST and STX, apparently have distinct roles in the development of neural cells is provided by using a neurite outgrowth assay.     

Model of bicarbonate secretion by resting frog stomach fundus mucosa I. Transepithelial measurements

In the present in vitro experiments on gastric fundus mucosa of Rana esculenta we try to define the mechanism of alkaline secretion that is observed in summer frogs in the resting stomach (blockage of HCl secretion by ranitidine, 10^–5 mol/l). The transepithelial voltage and the rate of alkalinization (ASR) of an unbuffered gastric lumen perfusate was measured as a function of serosal (and mucosal) fluid composition. ASR was high (0.88±S.E. 0.09 Eq·cm^–2·h^–1, n=11) during serosal bath perfusion with HCO₃ ^–-Ringer solution, decreased slightly to 0.50±0.07 Eq·cm^–2·h^–1 (n=6) in HCO₃ ^–-free HEPES-buffered Ringer solution of the same pH, and decreased to approximately 20% when carbonic anhydrase was inhibited by acetazolamide. While replacement of mucosal or serosal Cl^– did not — within 1 h — significantly alter ASR, replacement of serosal Na⁺ in the presence or absence of HCO₃ ^– strongly reduced ASR, and a similar reduction was observed after serosal application of the anion transport inhibitor DIDS (4,4-diisomiocyanatostilbene-2,2-disulphonate, 2·10^–4 mol/l), the metabolic poison rotenone (10^–5 mol/l), the uncoupler dinitrophenol (10^–4 mol/l), and the Na⁺ pump inhibitor ouabain (10^–4 mol/l), while serosal amiloride (10^–4 mol/l) had no effect. These data can be accounted for by a model of alkaline secretion that consists of basolateral HCO₃ ^– uptake from the serosal fluid into the cell via a DIDS-inhibitable Na⁺(HCO₃ ^–)_n-cotransporter and HCO₃ ^– secretion from the cell to the gastric lumen via an anionic conductance pathway. Microelectrode experiments on oxyntopeptic cells reported in the subsequent paper suggest that these cells may also be involved in the resting state alkaline secretion.