Serum from patients with chronic obstructive pulmonary disease promotes proangiogenic behavior of the vascular endothelium.

OBJECTIVE: It has been documented that COPD is a risk factor for lung cancer. In COPD patients, changes in lung angiogenesis - a critical process in the development of lung cancer - have been poorly investigated. We aimed to determine whether serum from COPD patients could promote the proangiogenic capabilities of endothelial cells in vitro. PATIENTS AND METHODS: The research was carried out using sera from COPD patients and healthy volunteers, endothelial cells EA.hy926, and bronchial epithelial cells. The concentration of angiogenic molecules was quantified using ELISA tests. The proliferation and migration of EA.hy926 were tested using fluorescence-based methods. Tube formation was analyzed with a commercially available assay. RESULTS: Sera from COPD patients and conditioned media generated by epithelial cells exposed to these sera stimulate proliferation, but not migration, of EA.hy926. This coincided with increased tube formation in both experimental regimens. The sera from COPD patients contained increased levels of CCL2, CCL21, and HGF, whereas the conditioned media generated by epithelial cells treated with these sera exhibited increased levels of CCL2, CCL21, CXCL8, FGF, and sICAM-1. The concentration of angiogenic markers in the sera and conditioned media, and their effect on the behavior of the endothelium were independent of smoking status (COPD and controls), stage of obstruction, and disease group (COPD). CONCLUSIONS: The increased incidence of lung malignancy in COPD patients may be associated, at least to some extent, with the direct and indirect proangiogenic activity of their sera (via alterations in the secretome of epithelial cells).

Development of porcine transgenic nuclear-transferred embryos derived from fibroblast cells transfected by the novel technique of nucleofection or standard lipofection.

The aim of our study was to determine the in vitro developmental potential of porcine nuclear-transferred (NT) embryos that had been reconstructed with Tg(pWAPhGH-GFPBsd) transgene-expressing fibroblast cells. The gene construct was introduced into fibroblast cells by the novel method of nucleofection or standard lipofection. NT oocytes derived from foetal and adult dermal fibroblast cells were stimulated by either simultaneous fusion and electrical activation (Groups IA and IB) or sequential electrical and chemical activation (Groups IIA and IIB). The percentages of cloned embryos that reached the morula and blastocyst stages were 152/254 (59.8%) and 77/254 (30.3%) or 139/276 (50.4%) and 45/276 (16.3%) in Groups IA or IB, respectively. The rates of NT embryos that developed to the morula and blastocyst stages were 103/179 (57.5%) and 41/179 (22.9%) or 84/193 (43.5%) and 27/193 (14.0%) in Groups IIA and IIB, respectively. In conclusion, the in vitro developmental competences of porcine transgenic NT embryos that had been reconstructed with the Tg(pWAPhGH-GFPBsd) gene-transfected fibroblast cells were relatively high. Further, the nucleofection efficiency of all the porcine fibroblast cell lines as estimated by intra-vitam fluorescent evaluation based on the index of reporter eGFP transgene expression was nearly 100%. However, PCR analysis for transgene screening confirmed the absence of Tg(pWAPhGH-GFPBsd) fusion gene in some of the nucleofected cell lines. To our knowledge, the novel method of nucleofection is the first to transfect nuclear donor cells in the production of transgenic cloned embryos.

Evaluation of screening procedures for congenital cataracts.

AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.

Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up.

UNLABELLED: Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. PURPOSE: To study the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skåne counties. METHODS: Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. RESULTS: Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. CONCLUSION: Neonatal screening is of importance to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with paediatricians.

The effects of tetrachloroguaiacol on the growth, survival, and development of the fathead minnow, Pimephales promelas.

Fathead minnow (Pimephales promelas) larvae were exposed for 7 days to tetrachloroguaiacol (TeCG), within 24 h of hatching, at concentrations of 0, 25, 50, 100, 200, 400 microg/L. No significant difference in growth or larval survival was found among treatments. Embryos, within 24 h of fertilization, were also exposed to TeCG at concentrations of 0 and 100 microg/L for 10 days. No significant difference was found between the control and treatment groups for larval survival, body length, body width, or for yolk size of the eleutheroembryos. However, a significant difference was found in the hatching success of the eggs (p = 0.05). Since fathead minnows have been known to spawn in areas close to sites that discharge bleached kraft mill effluent (BKME) which contains TeCG, into receiving waters, naturally occurring populations will likely be affected by the toxicant.

Joubert syndrome associated with Leber amaurosis and multicystic kidneys.

We describe a boy with manifestations of Joubert syndrome, Leber congenital amaurosis, and multicystic kidneys. In infants with unexplained neonatal tachypnea and late developmental delay, absence or hypoplasia of the cerebellar vermis should be sought. Joubert syndrome probably is an autosomal recessive disorder. In the subsequent pregnancy of the propositus' mother, we were able to make a prenatal diagnosis of Joubert syndrome, one of the first to be reported.

Frequency and natural history of retinopathy of prematurity (ROP). A prospective study in a Swedish city 1986-1990.

Frequency and natural history of retinopathy of prematurity (ROP) were prospectively studied in 142 preterm infants with birth weight (BW) less than 1501 g and/or gestational age (GA) below 33 weeks, who were born in Malmö 1986-1990. ROP developed in 27 (19%) of the 142 infants. The frequency of the ROP was significantly higher in infants with BW < or = 1000 g (54%) and in those with GA < or = 28 weeks (40%) than above these values. Infants with ROP had, compared with those without ROP, significantly lower BW, lower GA, lower Apgar score at 1 and 5 min, longer period of oxygen-therapy and higher frequency of neonatal complications. Five infants with stage 3 ROP were treated with cryotherapy; four with moderate changes showed good regression, the fifth with a severe stage 3 progressed and became blind. Up to 5 years follow-up revealed a significantly higher frequency of strabismus (40% vs 8%), myopia (25% vs 4%), and amblyopia (33% vs 6%) in infants with ROP than in those without ROP. Astigmatism and anisometropia were also frequent in children with ROP.

Takayasu's aortitis with renovascular hypertension.

We report a case of Takayasu's disease with severe renovascular hypertension in a girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation rate had normalized, reconstructive vascular surgery was performed as further progression of the disease seemed unlikely. However, probably due to her growth, the graft rotated and a second operation was successfully performed.

Generation of free oxygen radicals from human polymorphonuclear granulocytes by cytokines from human mononuclear cells, treated with quartz dust DQ12 or coal mine dust TF-1--new aspects in pathogenesis of pneumoconiosis.

We report about the release of a soluble mediator(s) from cultured human monocytes/macrophages after exposure to quartz dust DQ12 or coal mine dust TF-1. This mediator(s) activates isolated human polymorphonuclear granulocytes (PMN) to generation of free oxygen radicals. The strong and long-lasting production of reactive oxygen species (ROS), especially of superoxide anion, was measured as lucigenin dependent chemiluminescence (CL). Studies of mediator exposed PMN with the NBT-test (nitroblue-tetrazolium test) also demonstrated the strong activation of PMN. Electromicroscopical studies of mediator exposed PMN showed strong chemotactic changes in a time dependent manner and suggested the release of lysosomal products. According to these properties we called the mediator(s) "granulocyte activating mediator(s)" (GRAM). Biochemical characterisation indicated a protein nature of GRAM. High pressure liquid chromatography (HPLC) gel-filtration suggested that two molecules or two fragments of one molecule with a m.w. of about 20 kda and just below 10 kda resp. were responsible for the observed effects. PMN are potent inflammatory cells, which are known to immigrate in the lung tissue, especially in the early phases of silicosis. ROS released by activated PMN can act tissue destroying, mutagenic and are probably involved in collagene synthesis by regulation of activity of prolylhydroxylase. Mediator induced release of ROS seems to be an important event in development of lung fibrosis and presents a new mechanism of quartz dust and coal mine dust fibrogenicity.

Carcinogenesis from the standpoint of view of molecular geometry and synergism: relevance of oxygen and magnesium.

An attempt at a unified explanation of carcinogenesis, comprising physical, chemical and viral agents which are mutually synergistic involves the idea that continually replicated partially denatured chromosomal DNA carries the cancer genetic information. The evidence is circumstantial to date. While interactions and reactions of various heterogeneous chemical agents and absorption of radiant energy are detrimental to the helicity of the DNA, the interactions of magnesium and oxygen seem to be beneficial and thus may protect against cancer. Mechanisms for the damaging effects of various carcinogenic agents as well as for the protective effects of magnesium and oxygen are proposed. The increasing probability of cancer with age could be due to the cumulative actions of diverse carcinogenic agents. Some experimental results in vitro which are relevant to this hypothesis are discussed.