Hemolytic anemia, recurrent metabolic acidosis, and incomplete albinism associated with glutathione synthetase deficiency

The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree relatives. The relationship of these disease manifestations to the underlying metabolic defect is discussed.     

Characterization of Thy-1 (CDw90) expression in CD34+ acute leukemia

Thy-1 (CDw90) is a phosphatidylinositol-anchored cell surface molecule which, when coexpressed with CD34 in normal human bone marrow, identifies a population of immature cells that includes putative hematopoietic stem cells. To date, the characterization of Thy-1 expression has been confined largely to normal tissues and cell lines. In this study, we evaluated the frequency and intensity of Thy-1 expression as defined by reactivity with the anti-Thy-1 antibody 5E10 in 38 cases of CD34+ acute leukemia (21 acute myelogenous leukemia [AML], 8 chronic myelogenous leukemia [CML] in blast crisis, and 9 acute lymphoblastic leukemia [ALL]). In 34 of 38 cases (89%) the CD34+ cells lacked expression of the Thy-1 antigen. High-density Thy-1 expression was found in 1 case of CML in lymphoid blast crisis, and low- density Thy-1 expression was identified on a portion of the leukemic cells in 2 cases of AML with myelodysplastic features, and 1 case of CML in myeloid blast crisis, suggesting a possible correlation between Thy-1 expression and certain instances of stem cell disorders such as CML and AML with dysplastic features. In contrast, the dissociation of Thy-1 and CD34 expression in the majority of acute leukemias studied suggests that the development of these leukemias occurs at a later stage than the hematopoietic stem cell. Characterization of Thy-1 expression in acute leukemia may eventually provide insights into the origin of the disease. In addition, separation of leukemic blasts from normal stem cells based on Thy-1 expression may prove useful in assessing residual disease, as well as in excluding leukemic blasts from stem cell preparations destined for autologous bone marrow or peripheral stem cell transplantation.     

Expression of NK-lineage markers on peripheral blood lymphocytes with T- helper (Leu3+/T4+) phenotype in B cell chronic lymphocytic leukemia

Heterogeneity within lymphocyte subsets expressing T-helper (T4+/Leu3+) or T-suppressor (T8+/Leu2+) markers was analyzed in 38 patients with B cell chronic lymphocytic leukemia (B-CLL) and in 11 age-matched controls. Co-expression of NK-lineage markers (M1, Leu7) on Leu2+ or Leu3+ cells was investigated by two-color immunofluorescence, and the proportion of granular lymphocytes within each subset was determined by cytochemical staining for acid phosphatase. B-CLL patients and normal controls had similar absolute numbers of cells per microL with T- suppressor phenotype. However, the proportion of Leu2+ cells co- expressing the Leu7 antigen was higher in the B-CLL patients than in the control subjects (54 +/- 3% v 27 +/- 4%, P less than .0001). The absolute number per microL of cells with T-helper phenotype was somewhat decreased in B-CLL patients compared with normal subjects (649 +/- 104 v 799 +/- 33, P less than .02), with a consequent decrease of the helper/suppressor ratio. Furthermore, co-expression of the Leu7 and, more strikingly, of the M1 markers was increased significantly on Leu3+ cells from B-CLL patients compared with normal controls (11 +/- 2% v 2 +/- 0.7%, P less than .002 for Leu7 and 40 +/- 5% v 4 +/- 1%, P less than .00001 for M1). Cytochemical studies showed that a large proportion of Leu3+ cells from B-CLL patients were granular lymphocytes, as suggested by the co-expression of natural killer (NK) cell markers. The emergence of a population of Leu3+ granular lymphocytes with NK markers, which is barely detectable in normal subjects, may provide an explanation for the impairment of T cell functions repeatedly described in B-CLL.     

Identification of high-affinity (Kd 0.35 mumol/L) and low-affinity (Kd 7.9 mumol/L) platelet binding sites for ADP and competition by ADP analogues

Steady-state binding of ADP to blood platelets and isolated membranes has not previously been obtained because of complications arising from metabolism of the ligand and dilution due to its secretion from storage granules. In the present studies, competition binding isotherms (n = 9) using paraformaldehyde-fixed platelets showed that [2-3 H]ADP bound to two sites with a small amount (approximately 5% of total) of nonspecific binding: 410,000 +/- 40,000 sites of low affinity (Kd 7.9 +/- 2.0 mumol/L) and 160,000 +/- 20,000 sites of high affinity (Kd 0.35 +/- 0.04 mumol/L) corresponding to the ADP concentration required for activation in fresh platelets (0.1-0.5 mumol/L). All agonists and antagonists examined were able to compete with ADP at the high-affinity site. The strong platelet agonists 2-methylthio ADP and 2-(3- aminopropylthio)ADP competed with ADP at the high-affinity site with dissociation constant values of 7 mumol/L and 200 mumol/L, respectively. The partial agonist 2',3'-dialdehyde ADP and the weak agonist GDP also competed at the high-affinity site with Kd values of 5 mumol/L and 49 mumol/L, respectively. The sequence of binding affinities of other adenine nucleotides at the high-affinity site corresponded to their relative activities as known antagonists of platelet activation by ADP; namely, ADP(Kd 0.35 mumol/L) approximately equal to ATP (Kd 0.45 mumol/L) much greater than AMP (Kd 360 mumol/L). Adenosine and 2-chloroadenosine did not compete with ADP. ADP binding to the high-affinity site was inhibited by p-mercuribenzene sulfonate (Ki 250 mumol/L) but only very weakly by 5'-p- fluorosulfonylbenzoyladenosine (Ki 1 mmol/L). All the above nucleotides also competed with ADP at the low-affinity sites but, because of the high concentrations of competing nucleotide required, dissociation constants at this site were obtained only for ATP (21 mumol/L), 2-MeS ADP (200 mumol/L) and 2',3'-dialdehyde ADP (270 mumol/L). 8-Bromo ADP competed strongly with ADP at the high-affinity site (Kd 0.40 mumol/L) but weakly if at all at the low-affinity site. 8-Bromo ADP inhibited platelet activation induced by ADP (EC50 approximately 100 mumol/L) but not by collagen, thrombin, or ionophore A23187.(ABSTRACT TRUNCATED AT 400 WORDS)     

人工髓核假体置入治疗腰椎间盘突出症的疗效分析

目的：观察已在临床初步开展起来的人工髓核置换术治疗腰椎间盘突出症的中、远期临床疗效及并发症,分析其对策。 方法：纳入2002-02/2004-08南方医科大学附属南方医院脊柱骨病外科采用单枚人工髓核假体置换术治疗单节段腰椎间盘突出症患者98例,获得24～48个月随访患者75例,按平均随访时间达24,36,48个月,分为24个月组（n=30）,36个月组（n=23）,48个月组（n=22）。选同期采用单纯椎间盘髓核摘除术患者30例作为对照组,评估各组术后临床疗效,主观症状采用Oswestry功能障碍指数问卷表（0%表示正常,越接近100%则功能障碍越严重）和Prolo功能评分表（小于或等于5分为差,6～7分为中等,8～10为优）评价,分析术后影像学检查并测量手术节段活动度和椎间隙高度变化情况,同时观察假体位置情况,腰椎MRI观察假体位置和软骨终板的信号变化情况。腰椎活动度=（腰椎中立角度-前屈角度）＋（后伸角度-腰椎中立角度）=后伸角度-前屈角度;为消除X射线放大率的影响,椎间隙高度变化情况采用病变椎间隙后缘高度与上位椎体中部矢状径的比值表示。 结果：75例获得24～48个月随访者,全部进入结果分析。①48个月组2例、36个月组1例发生假体脱出,二次手术取出。其余患者术后临床症状均明显缓解,疼痛消失。②24,36,48个月组及对照组术后末次Oswestry功能障碍指数均较术前降低,差异有显著性意义（14.2%,52.1%;15.5%,55.2%;15.1%,53.6%;15.5%,51.5%;P〈0.05）。③24,36,48个月组及对照组术后末次Prolo能评分均较术前升高,差异有显著性意义（8.5,4.6分;8.6,4.5分;8.7,4.3分;8.4,4.2分;P〈0.05）。④24,36,48个月组同期手术节段腰椎活动度均高于对照组,差异有显著意义（P〈0.05）。⑤24个月组手术节段椎间高度较术前降低约4%、36个月组降低约12%、48个月组降低约18%、对照组较术前降低约25%,各组术前和术后椎间隙高度比值比较,差异具有显著性意义（P〈0.05）。⑥主要并发症：早期出现术后一过性腰痛24例,假体脱出3例。中、远期发现假体下沉32例,软骨终板损伤39例。 结论：单枚人工髓核假体置换治疗腰椎间盘突出症中、远期随访临床疗效肯定,但存在较严重并发症,应慎重开展此项手术。     

The prevalence of immunization to Duffy antigens in a population of known racial distribution

A retrospective study at our hospital determined the race or ethnicity of patients seen in an 8-year period who had formed antibodies to Duffy antigens. During that time, 9876 serologic investigations had been performed as a result of a positive direct or indirect antiglobulin test. Among these samples, sera from 45 previously transfused or pregnant patients contained anti-Fya and two contained anti-Fy3. Twenty-nine of the sera that contained anti-Fya (62%) were from blacks, 12 (25%) were from whites, and 6 (13%) were from Hispanics. Both examples of anti-Fy3 were made by black patients. Red cells (RBCs) from 21 of the black patients were Fy(a-b-), those from 7 were Fy(a-b+), and those from 1 could not be phenotyped. RBCs from 17 of the non-black patients were Fy(a-b+) and those from 1 could not be phenotyped. The population of transfused patients evaluated in this study was 47 percent black, 29 percent white, and 24 percent Hispanic. Calculations based on an expected Fy(a-) frequency of 88 percent in blacks, 33 percent in whites, and 20 percent in Hispanics predict that the racial makeup of the Fy(a-) population at our hospital would be 73 percent black, 18 percent white, and 9 percent Hispanic, which is not significantly different (p = 0.25) from the racial makeup of the patients forming anti-Fya and -Fy3. These data indicate that blacks make antibodies to Duffy antigens as frequently as non-blacks.     

人参皂甙Rb_1和Rg_1对小鼠中枢神经递质受体和脑内蛋白质合成的影响

应用放射配基结合法测定了人参皂甙Rb_1和Rg_1对α_1,α_2,β肾上腺素能受体、M胆碱能受体、5-羟色胺、多巴胺及GABA等七种受体的作用。结果均不能证明它们对这七种受体有亲和力。但给动物ip药物连续5天,Rb_1和Rg_1均能使中枢M胆碱受体密度显著增高。Rb_1及Rg_1还能显著增加脑内蛋白质的含量。上述实验结果对解释人参的中枢作用提供了重要证据。     

柯萨奇-腺病毒受体在肾癌组织中的表达及意义

目的:研究柯萨奇-腺病毒受体(CAR)在肾癌组织中的表达及意义.方法:应用免疫组化SP法检测12例癌旁正常肾组织和48例肾细胞癌组织中CAR的表达.结果:12例正常肾组织全部表达CAR,48例肾细胞癌组织中31例无CAR表达.不同分级CAR表达率分别为Ⅰ级54.5%(12/22)、Ⅱ级23.5%(4/17)、Ⅲ级11.1%(1/9);不同分期CAR表达率分别为Ⅰ期57.9%(11/19)、Ⅱ期30.8%(4/13)、Ⅲ期18.2%(2/11)、Ⅳ期0(0/5).结论:在多数肾细胞癌组织中CAR基因表达丧失;CAR表达变化与肾癌的分级、分期相关,可以作为肾癌分化、转移的重要生物学指标.     

The formation and function of the neutrophil phagosome

Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate.