Differential Effects of Thalidomide on Angiogenesis and Tumor Growth in Mice

Thalidomide, clinically used as an antiinflammatory and antitumoral drug, inhibited sponge-induced angiogenesis when administered systemically (100 mg/kg^–1) in mice. However, it failed to inhibit solid Ehrlich tumor in the same mouse strain. We have used functional, biochemical and histological parameters to assess neovascularization and fibrovascular tissue infiltration of the mice sponge granuloma. The neovascularization growth as detected by development of blood flow and hemoglobin content extracted from the implants showed that thalidomide inhibited fibrovascular tissue formation by 40%. The functional and biochemical parameters correlated well with the histological study. Thalidomide had no inhibitory effect in the development of Ehrlich tumor. The detection of this selective action using the same animal strain bearing two different processes, supports the hypothesis that rather than species specificity, thalidomide is tissue specific. This approach may be used to identify the specificity of other therapeutic agents against distinct angiogenesis-dependent diseases.     

The gene encoding CD23 leukocyte antigen (FCE2) is located on human chromosome 19

Using Southern blot analysis of DNAs from human×rodent cell hybrids, we have mapped the CD23 leukocyte antigen gene (FCE2) to human chromosome 19.     

Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B)

Sanfilippo B syndrome is caused by a deficiency of alpha-N- acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.      

Pneumococcus observatory data in the Rhône-Alps region. Results from 1996

Throughout 1996, 22 hospital-based laboratories in the Rh?ne-Alpes region of France collected pneumococcal strains and used a standardized protocol to record the following data; patient age and sex; type of specimen; and determination of susceptibility to at least the following antibiotics: oxacillin 1 microgram and 5 micrograms, erythromycin (Ery), tetracycline (Tet), chloramphenicol (Chl), rifampin (Rmp), and loracarbef. For penicillin-nonsusceptible strains (PNSSs), which were identified based on results with oxacillin, MICs for penicillin G, amoxicillin (Amx), and cefotaxime (Ctx) were determined using the E Test, at the study site and agar dilution at the coordinating center. Of the 1153 strains, 65.5% were from adults and 31.8% from children; patient age was unknown in 2.7% of cases. PNSPs (MIC > 0.06 mg/l) contributed 32.9% of strains (I: 23.3%; R: 9.6%) and were more common in children (41.1%) than in adults (28.1%). The frequency of PNSSs varied across specimen types: 27.9% in blood cultures (305 strains), 15.6% in cerebrospinal fluid (32), 38.7% in protected bronchopulmonary specimens (31), 31.5% in unprotected bronchopulmonary specimens (434), 50.8% in acute otitis media (118), and 34.4% in other specimens (221). Among PNSSs, nonsusceptibility (I + R) to other antibiotics was variable: Ery, 62.1%; Tet, 41.5%; Chl, 40.4%; Rmp, 1.1%. Corresponding figures for the overall strain population were Ery, 33.3%; Tet, 22.7%; Chl, 22.8%; Rmp, 0.9%. In addition, 56.5% of PNSSs exhibited multiple drug resistance. Resistance to amoxicillin (MIC > 2 mg/l) was demonstrated for only 5 strains. No strains were resistant to loracarbef or cefotaxime. Serotypes of the 379 PNSSs were as follows: 23F, 26.6%; 14 (25.6%); 9V (18.2%), 6 (8.7%), 15 (5%), 19 (4.5%).     

The vigilance-promoting drug modafinil counteracts the reduction of tyrosine hydroxylase immunoreactivity and of dopamine stores in nigrostriatal dopamine neurons in the male rat after a partial transection of the dopamine pathway

We studied the ability of the vigilance-promoting drug modafinil to modulate the anterograde and retrograde changes in tyrosine hydroxylase (TH) immunoreactivity and in dopamine (DA) stores in the nigro-neostriatal DA neurons, following a partial hemitransection of this ascending DA system, using a combined morphometrical, biochemical and behavioural analysis. Modafinil was given daily i.p. in doses of 10–100 mg/kg, starting 15 min after the lesion, and the partially hemitransected rats were killed 2 weeks later. Changes in TH-immunoreactive nerve cell bodies and nerve terminals induced by the partial hemitransection were studied in the substantia nigra and neostriatum in combination with image analysis. The substantia nigra and neostriatum were also subjected to biochemical analysis of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Modafinil treatment dose-dependently (10–100 mg/kg) counteracted the hemitransection-induced disappearance of nigral TH-immunoreactive nerve cell body profiles and neostriatal TH-immunoreactive nerve terminal profiles. A 2-week treatment with 100 mg/kg of modafinil also counteracted the hemitransection-induced depletion of DA stores in the neostriatum and the ventral midbrain. Moreover, the repeated daily treatment with modafinil (100 mg/kg) protected against the hemitransection-induced disappearance of striatal 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and noradrenaline levels. Striatal DA function was analysed by studying apomorphine-induced (1 mg/kg, s.c.) ipsilateral rotational behaviour 4 and 11 days after the operation. A marked dose-dependent reduction of ipsilateral rotational behaviour was demonstrated after the daily modafinil treatment in the partially hemitransected rats. In another model involving unilateral nigral microinjections of 6-hydroxydopamine, acute (one single dose) modafinil (100 mg/kg) did not affect the contralateral rotational behaviour induced by apomorphine (0.05 mg/kg s.c.), when given 30 min before the apomorphine. Taken together, morphological, neurochemical and behavioural evidence has been obtained that anterograde and retrograde changes induced in the DA stores and TH immunoreactivity of the nigro-neostriatal DA neurons by a partial hemitransection are counteracted by modafinil in a dose dependent way with 100 mg/kg producing a significant protective action against impairment of DA transmission. The results of this study open up the possibility that modafinil may protect against the anterograde and retrograde degeneration of nigrostriatal DA neurons seen after mechanically induced injury.     

Cytologic analyses of spindle-cell lesions of the thorax and retroperitoneum

Thoracic and retroperitoneal spindle-cell lesions represent a diagnostic challenge in the evaluation of fine-needle aspiration (FNA) specimens. The challenge is due to the morphologic similarities and wide variety of different entities with spindle-cell morphology in these two sites. The purpose of this study was to identify criteria helpful in the classification and differential diagnosis of spindle-cell lesions in these two locations. A set of cytologic features was analyzed in 57 thoracic or retroperitoneal spindle-cell lesions. Our results show that pleomorphism and abundant single cells were parameters associated with high-grade tumors in univariate and multivariate analysis, while coarse chromatin pattern was significant only in a univariate analysis. The combination of absence of pleomorphism, rare single cells, tight cluster arrangement, fine chromatin pattern, and absence of macronucleoli was seen only in benign cases. Assessment of background material was helpful in the differential diagnosis and classification. Necrosis was only found in high-grade cases.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

海南省大劣按蚊实验室自然交配的驯化研究

目的 建立实验室大劣按蚊自然交配繁殖种群,为同类研究提供依据。方法 将野外捕捉并在实验室人工交配繁殖至第61代的大劣按蚊,按不同雌雄比例先后顺序置于大、中、小三种不同型号的蚊笼中喂养、驯化、观察产卵情况并计算产卵数和孵化率。结果 在大、中、小蚊笼内的分别驯化至第15、10和18代时成蚊卵的孵化率各达到82％、83．4％和80．7％,成功建立小蚊笼自然交配的大劣按蚊种群。结论 经实验室驯化的大劣按蚊能够自然交配、产卵、繁殖,有助于建立实验室自然种群。     

甲状腺机能亢进症危险因素病例对照研究

目的 探讨各危险因素与甲亢的关系。方法 对三亚地区110例甲亢采用1：2配比的病例对照研究,资料处理采用条件Logistic回归分析.结果 甲亢发病与下列5因素关系密切：家庭年收入(OR=2．055)、食用碘盐(OR=2．133)、喜食海产品(OR=2．183)、感染(OR=2．382)、家庭生活事件(OR=3．017) 结论 家庭生活事件、感染、喜食海产品、食用碘盐、家庭年收入增高等是甲亢的危险因素。     

海南省性罪错妇女11年性病感染情况调查分析

目的 通过对11年来性罪错人员性病感染情况的调查分析,掌握性病在性罪错妇女中流行的特点,为政府部门对性病防治政策的制定提供科学依据。方法 对1990年元月至2000年12月海南省妇女收容教育所被收教的性罪错妇女进行性病检查,统计其各种性病的发病人数,然后进行分析。结果 11年中共收教4780人,其中感染淋病、非淋菌性尿道炎(宫颈炎)、尖锐湿疣、梅毒、生殖器疱疹、HIV共2967例,阳性率为62．07％,其中非淋菌性尿道炎(宫颈炎)1826例(38．20％)、淋病469例(9、81％)、梅毒414例(8．7％)、尖锐湿疣246例(5．14％)、生殖器疱疹11例(0．23％)、HIV阳性1例(0．02%)。结论 性罪错妇女六种性病的患病率很高,达62．07％,其中非淋菌性尿道炎(宫颈炎)为其主要病种,淋病的患病率逐年下降,梅毒的患病率逐年上升,尖锐湿疣基本稳定,其流行特点值得我们重视。