An integration of schizophrenia with schizotypy: identification of schizotaxia and implications for research on treatment and prevention

The liability to schizophrenia (schizotaxia) is associated with deficits in a variety of domains, including negative symptoms and neuropsychological deficits, even in the absence of psychosis or pre-psychotic prodromal symptoms. Conceptually, this view of schizotaxia is similar to negative schizotypy (i.e., schizotypal personality disorder minus the positive symptoms). It is broader than DSM-IV schizotypal personality disorder (SPD), however, in that more relatives of patients with schizophrenia show core symptoms of schizotaxia than meet the diagnostic criteria for SPD. Three lines of evidence support the validity of schizotaxia. First, evidence of concurrent validation was obtained by showing that schizotaxic subjects were more impaired than non-schizotaxic subjects on a variety of independent clinical scales. Second, schizotaxic subjects showed higher levels of negative symptoms on the Structured Interview for Schizotypy than non-schizotaxic subjects, but did not differ on positive symptoms. Third, subjects who met predetermined criteria for schizotaxia (i.e., negative symptoms and neuropsychological deficits) showed positive effects following treatment with low doses of risperidone (0.25-2.0 mg). Thus, clinical deficits in schizotaxia may be identifiable, and to a significant extent, reversible. Implications for the conception of schizotypy and the prevention of schizophrenia will be discussed.     

N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine formation by peroxidative metabolism

N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to play an important role in initiation of benzidine-induced bladder cancer in humans. This report assesses the possible formation of this adduct by peroxidatic activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32P-post-labeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H synthase (PHS). The peroxidatic activity of PHS was compared with that for horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or 2'- deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-post- labeling, the enzymatic and synthetic adduct were extracted from PEI- cellulose plates and were shown to have the same HPLC elution profiles for the bisphosphate adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate adduct with nuclease P1 yielded a product that eluted at the same time from the HPLC (32P-dpG-ABZ). Additional experiments demonstrated that the PHS-derived 5'-monophosphate (dpG- ABZ) and 3'-monophosphate (dGp-ABZ) adducts were also identical to their corresponding synthetic standard. With comparable amounts of total ABZ metabolism, PHS produced approximately 40-fold more dGp-ABZ than horseradish peroxidase (1943 +/- 339 versus 49 +/- 7.8 fmol/mg dGp). Adduct formation was dependent upon the presence of peroxidase and the specific substrate, i.e. arachidonic acid or H2O2. Adduct formation by PHS was inhibited by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not by 5,5-dimethyl-1-pyrroline N- oxide (DMPO) (100 mM), a radical scavenger. Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ. The mechanism of dGp-ABZ formation by PHS and horseradish peroxidase may be different.      

Characterization of reactions after transfusion of cellular blood components that are white cell reduced before storage

Background: During the storage of cellular components before transfusion, cytokines that may mediate transfusion reactions are released from white cells (WBCs). Adverse effects of transfused cellular blood components therefore depend not only on the number of residual WBCs in blood components, but also on the timing of WBC reduction. Study Design and Methods: Febrile nonhemolytic transfusion reactions (FNHTRs), allergic reactions, and other reactions were characterized in recipients of 4728 units of red cells (RBCs) and 3405 bags of single-donor apheresis platelets (SDAPs), all of which underwent prestorage WBC reduction. To delineate the impact of prestorage versus poststorage WBC reduction of RBCs on transfusion reactions, these results were compared with reactions occurring after the transfusion to similar recipients of 6447 bags of RBCs that underwent poststorage WBC reduction by bedside filtration and 5197 units of SDAPs that underwent prestorage WBC reduction. The levels of interleukin (IL) 1 beta, IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in a subset of 20 implicated cellular blood components at the time of transfusion reactions and correlated with the duration of storage before transfusion. Results: The incidence of reactions was greater after transfusions of SDAPs (5.49%) than of RBCs (1.63%). The incidence of FNHTRs after transfusion of RBCs that were WBC reduced before storage (1.1%) was significantly lower (p = 0.0045) than that after transfusion of RBCs that were WBC reduced after storage (2.15%). Although allergic reactions to RBCs that were WBC reduced before storage were also less common (0.41%) than those to RBCs that were WBC reduced after storage (0.51%), the difference was not significant (p = 0.067). At the time of reactions to RBCs and SDAPs that were reduced before storage, the level of IL-6 was negatively correlated (r = -0.54, p = 0.014) with the duration of storage before transfusion, and there was no correlation between the level of either IL-1 beta or IL-8 and the interval before transfusion. TNF-alpha was not detectable in any implicated component. Conclusion: FNHTRs, but not allergic reactions, were less common after transfusion of RBCs that were WBC reduced before storage than after the transfusion of those WBC reduced after storage at the bedside by filtration. The level of IL-6 in implicated cellular blood components that were WBC reduced before storage was inversely correlated with the length of storage before transfusion. Further studies are needed to determine whether the transfusion of cellular blood components that were WBC reduced before storage can both diminish the incidence of adverse reactions and improve outcome.     

周围神经再生与神经生长因子给药途径的关系

目的:应用周围神经损伤模型,局部和全身给予神经生长因子,观察对周围神经再生的影响。方法:实验于2001-06/2003-05在大连医科大学神经解剖研究室完成。选用体质量180～200gSD大鼠36只,随机分为3组,即全身用药组、全身对照组和局部用药组。其中局部用药组,右侧后肢为实验组,左侧后肢为对照组。切除大鼠5mm长的坐骨神经,两断端用硅胶管桥接形成再生室。局部用药组向右侧再生室内注入0.5mL神经生长因子;向左侧再生室内注入等量生理盐水为对照。全身用药组按5mL/kg腹腔内给药。对照组腹腔内注入等量盐水。术后9周对各组动物进行电镜观察及轴突计算机图像分析,采用辣根过氧化物法逆行追踪观察脊髓前角运动神经元的标记情况。结果:36只大鼠全部进入结果分析。①再生坐骨神经电镜观察结果:局部用药组及全身用药组的结果基本一致,有髓神经纤维髓鞘较厚、轴突直径较粗,髓鞘厚呈板层样排列,神经再生活跃。而对照组中有髓神经纤维髓鞘较薄、直径细小。②轴突计算机图像分析:用药组轴突数目优于对照组[局部:(2781±170),(1758±103)个/μm2;全身:(2840±127),(1786±112)个/μm2,P均<0.01];用药组轴突直径亦优于对照组[局部:(1.11±0.18),(0.64±0.17)μm,全身:(1.16±0.15),(0.87±0.17)μm,P均<0.01]。③辣根过氧化物酶标记结果:实验组脊髓腰段横切片中,可见较多标记的前角运动神经元,而对照组中则少见。全身用药组与局部用药组结果相似。结论:全身和局部应用神经生长因子对周围神经再生有明显的促进作用。神经生长因子也支持运动神经元存活。     

"Naturally Occurring" Anti-Kell (Kl): Two Examples

"Naturally occurring" anti-Kell(Kl) is reported for the first time and was found in the sera obtained from two male adults. The two examples of this antibody were detected as a result of routine screening of donors' blood for atypical antibodies. Both strongly agglutinated type K:l cells in saline solution at room temperature. The mechanism of formation of the anti-Kl was not known in either case.