Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.     

人乳头瘤病毒16型DNA转化人胚肺细胞的实验研究

人乳头瘤病毒(HPV)的16,18,31,33型等与宫颈癌的发病有关,其中HPV16与宫颈癌关系密切。为进一步研究HPV16的致癌性,我们用克隆的HPV16 DNA(2μg/10~5细胞)转染体外培养的人胚肺细胞,并进行了细胞存活时间、血清依赖性、着壁依赖性、间接免疫酶检测、HPV16 DNA、同源序列检测、染色体核型等生物学的研究。结果表明,转染细胞存活时间延长、在软琼脂培养基中形成集落、HPV16特异抗原得以表达、HPV16 DNA的同源序列存在于细胞中。表明本实验用HPV16DNA转染的人胚肺细胞具备转化细胞的某些特征,HPV16有使人胚肺细胞转化的作用。     

Insulin-like growth factor I promotes leiomyoma cell growth in vitro

Objective: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture.Study design: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture.Results: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factos II. Neither factor exerted a stimulatory effect on myometrial cells.Conclusion: Insulin-like growth factor sI preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracine role in vivo for this factor in conjuction with gonadal steroids in promoting leiomyoma growth.     

The effects of long-term, low-dose diazepam treatment on the guinea pig righting reflex and medial vestibular nucleus neuronal activity

Guinea pigs received a 2 mg/kg IP injection of diazepam, or an equivalent volume of vehicle, daily for 28–60 days. To determine whether tolerance developed to the ataxic effects of diazepam on the righting reflex, daily righting reflex latency (RRL) measurements were made before and 20, 30, and 40 min following the diazepam or vehicle injection for 28 days. Analyses of the RRLs for individual animals indicated that a significant decrease in RRL over time (indicating tolerance) occurred in only one out of nine animals receiving diazepam and in none of the vehicle animals. Medial vestibular nucleus (MVN) neurons in brain stem slices from animals receiving chronic diazepam treatment had a significantly higher average firing rate than those from vehicle controls. These results suggest that: a) long-term treatment with single 2 mg/kg daily IP injections of diazepam does not result in tolerance to diazepam's ataxic effects on the righting reflex in the majority of animals; b) this form of diazepam treatment may, nonetheless, induce a hyperactivity of brain stem MVN neurons that may be consistent with the occurrence of a withdrawal syndrome.     

In-vitro synthesis of steroid hormones in corpora lutea from normal women and women treated with 300 micrograms norethisterone.

The in-vitro oestradiol (E2) and progesterone (P) production by corpora lutea (CL) obtained at sterilization from 30 untreated women and 43 women treated with norethisterone (NET) 300 micrograms daily was measured. The CL were obtained at different stages of the luteal phase in the untreated women [luteinizing hormone (LH) 0 to +3, n = 7; LH +4 to +7, n = 7; LH +8 to +11, n = 9; LH +12 to menses, n = 7] and on days LH +8 to +11 or cycle days 22 to 26 in the NET-treated women. In the treated women, four types of ovarian reaction were identified. Four women showed ovarian reaction Type A (completely inhibited ovarian activity), 14 women Type B (marked follicular activity, but no luteal function), 12 women Type C (normal follicular activity, followed by insufficient luteal function) and 13 women Type D (apparently normal follicular and luteal activity). The CL were incubated in Eagle's medium with and without stimulation by human chorionic gonadotrophin (HCG) for 2 and 4 h. In the untreated women, P and E2 production increased significantly with both incubation time and stimulation by HCG throughout the luteal phase, except in the late luteal phase (LH +12 to menses) where P increased (P less than 0.01) only after 4 h stimulation by HCG. The maximal production of P was found after 4 h incubation with HCG stimulation of CL tissue in the early-mid luteal phase (LH +4 to +7).(ABSTRACT TRUNCATED AT 250 WORDS)     

钩端螺旋体核糖体提取物免疫保护作用的研究

作者对核糖体现有的制备方法进行了部分改进,从黄疸出血群赖型017株钩体中成功地制备了核糖体提取物。该提取物经SPA-ELISA 证实具有免疫原性,对40只受试豚鼠的保护试验结果表明,核糖体提取物对同型毒株的攻击具有明显的保护作用;结果还证明核糖体提取物能诱导机体的体液免疫反应。     

Effects of hydroxocobalamin on rat cardiac papillary muscle

Hydroxocobalamin is a rapid and powerful antidote in acute cyanide poisoning. The effects of hydroxocobalamin (0.1, 0.3, and 1 mM) on intrinsic myocardial contractility were studied on isolated rat cardiac papillary muscles (n=10). Whatever the concentration, hydroxocobalamin did not modify the active isometric force and a slight increase in maximum unloaded shortening velocity was noted at 1 mM. Only 0.3 mM significantly impaired contraction-relaxation coupling under low load, suggesting a slight decrease in sarcoplasmic reticulum function. No changes in contraction relaxation coupling under heavy load were noted, suggesting the lack of modification of myofilament calcium sensitivity. These results suggest that hydroxocobalamin does not induce noticeable changes in intrinsic myocardial contractility. An indirect mechanism might be involved in the previously reported decrease in cardiac function at supratherapeutic concentrations of hydroxocobalamin.     

High postovariectomy LH levels are not due to decreased opioid inhibition of GnRH

It has been proposed that endogenous opioid peptide (EOP) inhibition of hypothalamic GnRH secretion mediates and is dependent upon gonadal steroid feedback of LH secretion, although considerable conflicting data have been reported. Accordingly, a well-characterized replacement regimen was used to approximate physiological stimulation by estradiol (E2) and progesterone (P4) in adult rats 10 days after ovariectomy (OVX), followed by in vitro incubation of the isolated median eminence to evaluate the role of E2 and P4 in modifying GnRH release in response to the opiate receptor antagonist, naloxone (NAL). Basal (control) GnRH release from median eminences of OVX, OVX + E2, and OVX + E2 + P4 rats was similar, and NAL treatment elicited a comparable increase in GnRH release under all three gonadal steroid conditions. Thus, EOP suppression of median eminence GnRH secretion does not appear to mediate or be dependent upon negative feedback regulation of LH secretion by physiological concentrations of gonadal steroids.     

同型半胱氨酸对胚胎海马神经元细胞的影响

目的 观察同型半胱氨酸(homocysteine，HCY)对海马神经元细胞分化和增殖的作用机理。方法 采用大鼠胚胎海马神经元细胞进行体外培养。观察不同浓度的HCY(0．01、0．1、1．0、10．0、100．0)mmol／L对细胞分化和增殖的影响。结果 随着剂量的增加．同型半胱氨酸对胚胎海马神经元细胞分化和增殖具有抑制作用，并用流式细胞术分析证明对脂质过氧化(LPO)的影响而使得神经元蛋白质含量增高。结论 同型半胱氨酸可抑制胚胎海马神经元细胞分化和增殖的影响，HCY可能在导致神经管畸形的过程起着重要作用。     

Correlation between sperm penetration into the human zona pellucida and in vitro fertilization rates

Summary.  Sperm penetration into the zona pellucida of unfertilized oocytes, and its correlation with in vitro fertilization rates of the sibling oocytes, were assessed. This was performed in order to evaluate the prediction rate of the sperm penetration test into the zona pellucida. Unfertilized oocytes ( n =1872) from 371 cycles were pipetted through a microcapillary, and the remaining sperm cells penetrating the zona pellucida were counted. The mean (±SD) number of spermatozoa that penetrated the zona pellucida of unfertilized oocytes was 12.9±16.37. A significant correlation was found between the fertilization rate and the mean number of spermatozoa that penetrated into the zona pellucida of the unfertilized sibling oocytes (r = 0.48; P < 0.001), or the percent of unpenetrated zonae pellucidae in a cohort (r= —0.43; P < 0.001). However, a distinct variation in the number of spermatozoa that penetrated into the zona pellucida was detected. A step-wise regression analysis proved the number of spermatozoa penetrating the zona pellucida to be more predictive for fertilization rates than the variable of percent of unpenetrated zonae pellucidae. The results imply that although there is interdependence between penetration into the zona pellucida and fertilization rate, the predictive value of sperm penetration test for prognosis and future management after the first in vitro fertilization attempt, is limited.