F.G. syndrome: a rare and/or extremely polymorphic syndrome?

We report a case of mental retardation associated with multiple congenital anomalies suggesting an F.G. syndrome. We discuss problems concerning genetic counselling and the management of future pregnancies. Unfortunately, no concrete strategy, concerning prenatal diagnosis, can be proposed.     

Role of hypothalamic adenosinergic systems in regulating states of wakefulness in the rat

Immunohistochemical localization of adenosine deaminase (ADA), marker for the putative neurotransmitter/neuromodulator adenosine, has revealed a population of ADA-positive neurons in the ventrolateral hypothalamus in the rat brain. These posterior neurons possess adenosine uptake sites. We have studied the effects of local injections of adenosinergic drugs on the sleep-wake cycle in the rat. Microinjection of erythro-9-(hydroxy-2, nonyl-3) adenine (EHNA), a specific inhibitor of adenosine deaminase, resulted in a significant decrease in wakefulness (W) and an increase in deep slow wave sleep (SWS, or S2) and paradoxical sleep (SP). On the other hand, microinjections of soluflazine, a nucleoside transport inhibitor, increased W and decreased total sleep. These opposite modifications may reflect opposite variations in the extracellular concentrations of Ado and consequently different responses of A1/A2 adenosine receptors.     

Studies on the immunological cross-reactivity of various pancreatic colipases. Isolation by immunoaffinity chromatography of a single form of procolipase from porcine pancreas

Antibodies against porcine procolipase B were produced in rabbits. The antiserum was used to immunoinactivate various forms of native and trypsin-treated porcine colipase. Our results indicate that all forms of the porcine cofactor bind to anti-porcine procolipase B antibodies. Human colipase showed lower affinity for the antibodies than porcine colipase. No cross-reactivity was observed between pig and horse, cow, dog or chicken colipases. Immunological studies on porcine colipase, carried out in the presence of lipid, provided evidence that antibodies bind to colipase at or near the lipase binding site. The binding of antibodies to colipase is not affected by the adsorption of the cofactor at a lipid interface. Using a predictive method for identification of the antigenic determinants, it was found that, in pig colipase, regions at positions 42-48 and 70-74 might represent antigenic sites. In the horse protein, the peptide segment 42-48 was also recognized as a possible antigenic site. An immunoadsorbent gel column was prepared for a one-step isolation of porcine colipase. In contrast to purification methods described so far, immunoaffinity chromatography yielded only one form of the porcine cofactor when starting from a pancreatic extract. This protein preparation has structural, biochemical and immunochemical properties similar to that of porcine procolipase A previously isolated from pancreas in the presence of detergent.     

Biocalcification by <Emphasis Type="Italic">Bacillus pasteurii</Emphasis> urease: a novel application

Biocalcification, also known as microbiologically induced calcite precipitation (MICP), is a phenomenon involving the activity of the enzyme urease. A large number of soil microorganisms exhibit urease-producing ability. A novel application of MICP to improve properties of bricks by a soil bacteria Bacillus pasteurii NCIM 2477 was studied. Most of the deterioration of brick structures takes place because of the presence of moisture. Deposition of calcite on the surface and in voids of bricks reduces the water absorption substantially. A favorable effect of microbes to improve the durability of bricks by reducing water absorption was demonstrated as a novel concept in this paper.     

Specific recognition of macroscopic objects by the cell surface: evidence for a receptor density threshold revealed by micrometric particle binding characteristics

The establishment of specific molecular bonds between a cell and a facing surface is involved in many physiological and technological situations. Using micrometric magnetic particles, we have explored the formation of specific molecular bonds between the cell and surfaces bearing complementary ligands under passive conditions. Streptavidin-coated particles were targeted to the cell surface of a B-cell line through a specific biotinylated antibody against the CD19 receptor. Flow cytometry, optical microscopy, and micropipette experimental techniques have been used. Main findings have been that cell surface receptor density acted like a switch for particle capture with a threshold value found here equal to 1.6 x 10(3) receptor/ microm(2). This led to exclusion from binding of the cells of lowest receptor density. The density threshold was modulated by the length of the binding link and the physics of the cell/particle collision. We suggest that the shear stress is one of the main determinants of the characteristics of binding. We also show that several thousand receptors were involved in the cell particle contact at the end of the binding process, although only eight bonds are required for the initial capture of a particle. A passive binding inhibition process due to link concentration by the initial contact was proposed to account for the small number of particles per cell.     

Assessment of DNA damage in women using oral contraceptives

The effect of the use of an oral contraceptive (OC) on the frequency of sister chromatid exchanges (SCEs) and on the response in the alkaline comet assay (single-cell gel electrophoresis (SCGE)) was investigated in 18 women taking contraceptive pills daily for 24 months. As controls, fertile women were included with regular menstrual cycles who received no OC drugs. A significant increase in the number of lymphocytes with DNA migration and an increased frequency of SCE per metaphase were observed in OC users as compared with their age-matched untreated controls (P<0.005). As higher incidences of spontaneous SCEs in peripheral blood lymphocytes have been reported to occur in females during pregnancy due to profound changes in the levels of certain sex hormones such as progesterone and estrogen, particularly during the last trimester, 17 pregnant women served as positive controls in this study in order to test the rate of genetic damage due to those changes. Higher frequencies of SCEs and comet responses were observed in pregnant women than in their matched controls. However, no statistically significant difference in DNA damage was observed between OC users and pregnant women (P>0.05). This study underscores the fact that prolonged and extensive use of these drugs in our daily life may be hazardous and also, that OC users should be aware of multifactorial risk factors (environmental, genetic and life style patterns) that may be responsible for additional DNA damage.     

Chromosomal aberrations under basal conditions and after treatment with X-ray in human lymphocytes as related to the GSTM1 genotype

The frequency of chromosomal aberrations (CAs) was evaluated in blood lymphocytes from 18 healthy subjects. Basal CA frequencies were not significantly different in GSTM1 positive and GSTM1 null subjects (P>0.05), whereas they were considerably higher in smokers than in non-smokers. After 1 Gy dose of X-ray challenge of blood samples, CA frequencies were significantly higher in GSTM1 null subjects, compared to GSTM1 positive subjects (P<0.005), and in smokers, compared to non-smokers. These effects are ascribed to the influence of GSTM1 genotype and of smoking status on DNA repair capacities. As the induction of CAs are associated with carcinogenesis, the challenge assay is able to detect enhanced susceptibility for CA caused by genetic predisposition of DNA repair deficiency.     

Formation, Metabolism, and Action of Hepoxilin A3in the Rat Pineal Gland

Abstract: The present study was undertaken to investigate the possible formation of hepoxilin A₃ in the rat pineal gland and to study the potential physiological role for this compound in this tissue. Incubation of homogenates of rat pineal glands with arachidonic acid (66 μM) led to the appearance of hepoxilin A₃ (HxA₃) analyzed as its stable trihydroxy derivative, trioxilin A₃ by gas chromatography in both the electron impact and negative ion chemical ionization modes. Endogenous formation of HxA₃ is estimated to be 1.43 ± 0.66 ng//μg of protein. This amount is not modified when the tissue is boiled (2.07 ± 0.66 ng/μg of protein). However, the formation of this compound was stimulated to 21.26 ±5.82 ng/μg of protein when exogenous arachidonic acid was added to the homogenate. Addition of the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (10 /μg) resulted in a partial blockade of hepoxilin formation. Using [1-¹⁴C] H×A₃, we demonstrated that the pineal gland contained hepoxilin epoxide hydrolase, which hydrolyzed HxA₃ into trioxilin A₃. This hydrolysis was inhibited by 1 μmol/L of 3, 3, 3-trichloropropene-1, 2-oxide. In a separate study, HxA₃ in the presence of 3, 3, 3-trichloropropene-1, 2-oxide to block the hydrolysis of HxA₃ decreased the production of cyclic AMP in cultured organ rat pineals after stimulation with 5′-N-ethylcarboxamidoadenosine, an A₁/A₂ adenosine receptor agonist. This effect is stereospecific because the (8S)-enantiomer is more active in decreasing cyclic AMP production (?88.7%) than the (8R)-enantiomer. This is the first demonstration of the presence, metabolism, and action of HxA₃ in the rat pineal gland.