Rapid and high production of precipitating antibodies in rats.

Rats were inoculated into the foot-pads with 0.2–1 mg antigen mixed with complete Freund's adjuvant or Bordetella pertussis. When DNP-protein conjugates or heterologous immunoglobulins were used as antigen, serum concentrations of 1–2 mg antibody per ml were usually obtained after 11 days. After a booster injection, made in the same way, a few weeks later, much higher titres were frequently observed with most antigens. With microgram doses of antigen, good precipitating antibody production was observed only after booster injections.     

Cytogenetic forms of retinoblastoma: their incidence in a survey of 66 patients

Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.     

Effect of Paris Saponin on Antitumor and Immune Function in U14 Tumor-Bearing Mice

We evaluated the effect of Paris saponin on inhibition of cervical cancer in mice and on immune regulation in tumor-bearing mice. MTT assay was used to examine the effect of Paris saponin on U14 cell proliferatiosn in vitro; the ascites tumor model of U14 cervical cancer was established to observe the effect of Paris saponin on inhibition of the tumor and on survival time of mice; and serum IL-4 and IFN-γ levels in tumor-bearing mice were detected. The Paris saponin showed significant inhibitory effect on growth of cervical cancer U14 cells both in vitro and in vivo, prolonged the survival time of mice, increased the serum IFN-γ level of tumor-bearing mice, and reduced the serum IL-4 level. The Paris saponin can inhibit U14 cell growth and prolong survival time of mice; it is speculated that the Paris saponin may express its anti-tumor activity by improving the body''s immune system.     

Blood flow compensates oxygen demand in the vulnerable CA3 region of the hippocampus during kainate-induced seizures

Local blood flow, and partial pressures of oxygen and carbon dioxide were directly monitored in the vulnerable region of Ammon's horn (e.g. CA3) of unanaesthetized, freely breathing rats in which epileptic seizures of 120 min duration were induced by parenteral kainic acid. Blood flow was periodically determined by helium clearance. Partial pressures of oxygen and carbon dioxide were simultaneously and continuously measured by means of mass spectrometry, in order to determine if the neuronal damage occurring during the seizures were due to local hypoxia or if blood flow compensated the metabolic demand. During the wet shakes period, a decrease of 35% in the partial pressure of oxygen occurred, concomitant with an increase of 33% in the partial pressure of carbon dioxide and of 330% in local blood flow in Ammon's horn. During the limbic motor seizures, the partial pressure of oxygen increased progressively to twice its baseline value, while the partial pressure of carbon dioxide returned to its baseline value and blood flow underwent a six-fold increase. Thus the seizures produced by kainate do not lead to a mismatch between oxygen supply and blood flow. Our results provide direct evidence that hypoxia cannot be considered responsible for the damage produced by the seizures in CA3. It is concluded that brain damage in CA3 is due to an enhanced neuronal activity associated with the release of a toxic endogenous substance and an excessive rise of intracellular concentration of calcium.     

Sister chromatid exchanges in patients with retinoblastoma

Spontaneous and mitomycin C(MMC)-induced sisyer chromatid exchanges were studied in 11 patients with retinoblastoma and 7 normal controls. Spontaneous rates were similar in patients and in controls. The MMC-induced rate was found to be significantly higher in bilaterally affected patients than in controls. It is suggested that this increase may be due to a DNA repair deficiency. However, it is not possible to clarify wether this abnormality is associated with the retinoblastoma gene or with another factor acting on the degree of expressivity of the disease in gene carriers.     

Brachmann-de Lange syndrome. Delineation of the clinical phenotype

A total of 31 cases previously diagnosed as having Brachmann-de Lange syndrome were ascertained and examined, of which 11 were thought to have been misdiagnosed. Of those correctly diagnosed, there appeared to be a phenotypic dichotomy with classical and mild cases. Those facial findings of greatest diagnostic value were the combination of the characteristic eyebrows, long philtrum, thin lips and crescent-shaped mouth. The characteristic eyebrows were neat, well defined and arched as though they had been pencilled. This combination of anomalies was absent in postpubertal males but not in postpubertal females. Facial abnormalities most likely to lead to incorrect use of the eponym were hypertrichosis, synophrys, and bushy eyebrows. © 1993 Wiley-Liss, Inc.     

Translocation involving chromosome 22 in Ewing's Sarcoma. A cytogenetic study of four fresh tumors

Ewing's sarcoma was described in 1921 by James Ewing as a diffuse endothelioma of bone and, for some time, was believed to be an undifferenciated type of Parker's sarcoma. At present, these two entities are thought to be distinct, the macroscopic and microscopic aspects of Ewing's sarcoma being very characteristic, although the exact cell type of this tumor remains unknown. This has lead many workers to study this sarcoma in order to recognize its origin.We thought it of interest to carry out cytogenetic investigations of our cases of Ewing's sarcoma, since very few chromosomal data on this malignancy exist in the literature [1–3].     

Properties of the tobacco mosaic virus intermediate length RNA-2 and its translation

The existence of subgenomic RNAs is well established in the case of plant viruses such as tobacco mosaic virus (TMV). However, except for the subgenomic coat protein mRNA, it is not known whether the other subgenomic RNAs have a function in the life cycle of the virus. In search of more information about one of the major subgenomic RNAs-intermediate length RNA-2 or I2 RNA-of TMV, in vitro and in vivo translational studies were performed. The I2 RNA, which codes in vitro for the synthesis of a 30K (K = kilodalton) protein, appears to be uncapped as judged by the need of different in vitro translation conditions for the synthesis of this protein, compared to the conditions required for the synthesis of the 126K and 183K proteins coded by the capped genomic RNA. In vivo a protein migrating in the same position as the 30K protein synthesized in vitro can be detected in infected tobacco leaves. Since this protein occurs transiently early upon infection, whether it is virus-coded or virus-induced, it could have an early function during infection.     

Combination therapy with ciprofloxacin and third-generation cephalosporin versus third-generation cephalosporin monotherapy in Escherichia coli meningitis in infants: a multicentre propensity score–matched observational study

ObjectivesEscherichia coli is the second cause of bacterial meningitis in neonates. Despite the use for 35 years of third-generation cephalosporins (3GCs), high morbidity and mortality rates with E. coli meningitis continue to occur. Because ciprofloxacin has good microbiologic activity against E. coli and good penetration in cerebrospinal fluid and brain, some authors have suggested adding ciprofloxacin to a 3GC regimen. The objective of this study was to assess combining 3GCs with ciprofloxacin versus 3GCs alone in a cohort of infants with E. coli meningitis.MethodsWe included all cases of E. coli meningitis diagnosed in infants <12 months of age that were prospectively collected through the French paediatric meningitis surveillance network between 2001 and 2016. The main outcome was the proportion of short-term neurologic complications with versus without ciprofloxacin. The analysis was conducted retrospectively by multivariable regression and propensity score (PS) analysis.ResultsAmong the 367 infants enrolled, 201 (54.8%) of 367 had ciprofloxacin and 3GC cotreatment and 166 (45.2%) of 367 only a 3GC. Median age and weight were 15 days (range, 1–318 days) and 3.42 kg (range, 0.66–9.4 kg). A total of 86 (23.4%) of 367 infants presented neurologic complications (seizures, strokes, empyema, abscesses, hydrocephalus, arachnoiditis); 57 received ciprofloxacin cotreatment. Complications were associated with ciprofloxacin cotreatment on multivariable analysis (odds ratio (OR) = 1.9; 95% confidence interval (CI), 1.1–3.4) and PS analysis (OR = 1.9; 95% CI, 1.1–3.3). Mortality rate did not differ with and without ciprofloxacin: 22 (10.9%) of 201 versus 16 (9.6%) of 166 deaths (OR = 0.7; 95% CI, 0.3–1.6; PS analysis).ConclusionsCiprofloxacin added to 3GCs at least offers no advantage for neurologic outcome and mortality in infants with E. coli meningitis.     

Making Sense of the ‘Chemical Revolution’. Patients’ Voices on the Introduction of Neuroleptics in?the 1950s

The so-called chemical revolution has produced a vast historiographical corpus. Yet the patient’s voice remains surprisingly absent from these stories. Based on the archives of the Institut de Psychiatrie (Brussels), this paper traces the introduction of Largactil as recounted in patient letters, physician records and nurse notes. The paper thus contributes to the history of therapies from below, but also participates in the historiographical debate about whether the introduction of neuroleptics can indeed be considered a revolution.     

Retinoblastoma,deletion 13q14, and esterase D: Application of gene dosage effect to prenatal diagnosis

Esterase D (ESD) gene dosage studies were performed on amniotic cells from a fetus at risk for del 13q14. The mother was a balanced carrier of an insertion in chromosome #20: 46,XX,ins(20;13)(p12;q1307q14.3). She had already given birth to a monosomic child with retinoblastoma (Rb) and to a phenotypically normal child trisomic for the same 13q14 segment. Both sibs displayed the expected proportionate gene dosage effects for ESD. A 153% value of ESD activity was found in the amniotic cells indicating unambiguously that the fetus was not monosomic for segment 13q14 and therefore not at increased risk for Rb. The mother delivered a phenotypically normal child who was confirmed to be trisomic for segment 13q14 by cytogenetic analysis and by gene dosage studies for ESD in cord blood cells and in lymphoblastoid cells.     

Pelizaeus-Merzbacher disease caused by a de novo mutation that originated in exon 2 of the maternal great-grandfather of the propositus

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder of the central nervous system. Many cases of PMD can be attributed to defects in the proteolipid protein gene (PLP). To date, with one exception, each family has had either no or a unique mutation in one of the seven exons of PLP. We describe a new missense mutation in exon 2 of the PLP gene of an affected individual. This mutation codes for Ile instead of Thr at codon 42. The point mutation originated in the X chromosome of the maternal great-grandfather of the propositus. This was determined from the pattern of inheritance of the AhaII polymorphism and a series of microsatellite markers that are localized near PLP at Xq22. © 1995 Wiley-Liss, Inc.     

On the variability of the Brachmann-de Lange syndrome in seven patients

The results of the clinical and radiographic study of 7 patients support the view of a unimodal and rather narrow phenotypic spectrum in the Brachmann-de Lange syndrome (BDLS) and reject the existence of a “classic” type of patient and a “mild phenotype” without upper limb defects who survive with moderate to severe mental retardation. Similarity among all patients is greater than their phenotypic differences. Strict clinical definition of the syndrome warrants easier access to the still unknown cause, most probably a single gene mutation with autosomal dominant inheritance. © 1993 Wiley-Liss, Inc.     

重楼单体PP-11对人乳腺癌MDA-MB-231细胞增殖的抑制作用及其机制

目的:探讨中药重楼(Paris polyphylla,PP)活性单体PP-11体外抑制人乳腺癌MDA-MB-231细胞增殖的作用及其机制。方法:采用不同浓度的PP-11作用于MDA-MB-231细胞,采用MTT法和集落形成实验检测细胞增殖情况;Hoechst 33258染色及Annexin V-FITC/PI双染流式细胞术检测细胞凋亡;JC-1染色检测线粒体膜电位改变;Western blot法检测细胞凋亡及自噬相关蛋白表达情况。再采用总caspase抑制剂Z-VAD-FMK、p38抑制剂SB203580和自噬抑制剂氯喹(chloroquine,CQ)进行阻断实验。结果:MTT测定结果显示,PP-11以剂量和时间依赖方式显著抑制MDA-MB-231细胞活力,其作用24、48和72 h后的IC₅₀分别为5.64、4.58和3.06μmol/L。集落形成实验结果提示,PP-11显著抑制MDA-MB-231细胞集落形成。Hoechst 33258染色观察到PP-11组MDA-MB-231细胞出现典型的细胞凋亡形态。Annexin V-FITC/PI双染流式细胞术结果显示,随着PP-11浓度的增加,MDA-MB-231细胞凋亡率逐渐升高。JC-1染色结果显示,PP-11处理的MDA-MB-231细胞线粒体膜电位下降。Western blot检测结果显示,PP-11处理的MDA-MB-231细胞Bcl-2家族蛋白中抗凋亡蛋白Bcl-2和Bcl-xL的表达显著减少,促凋亡蛋白Bim和Bok表达增加,p-p38和p-p53蛋白水平升高,p-ERK蛋白水平降低,cleaved caspase-9、cleaved caspase-3及cleaved PARP的蛋白水平显著升高;PP-11降低MDA-MB-231细胞p-STAT3蛋白水平及其下游蛋白c-Myc、cyclin D和Mcl-1的表达。总caspase抑制剂Z-VAD-FMK和p38 MAPK抑制剂SB203580均可减弱PP-11诱导的细胞凋亡。随着PP-11作用浓度的增加,细胞自噬相关蛋白LC3-Ⅱ表达增加,p62/SQSTM1表达下降;采用PP-11联合自噬阻断剂CQ,可逆转PP-11诱导的cleaved PARP表达,并提高细胞活力(P<0.05)。结论:重楼单体PP-11可显著抑制人乳腺癌MDA-MB-231细胞增殖。PP-11通过激活p38 MAPK信号通路、抑制ERK和JAK-Stat3信号通路诱导MDA-MB-231细胞发生线粒体相关的凋亡,并促进细胞自噬。