Frequencies of chromosomal aberrations induced in human blood lymphocytes by low doses of X-rays

The dose-response for radiation-induced chromosome aberrations in human lymphocytes is usually fitted to the quadratic model. This assumes that the slope is essentially linear at low doses. Empirical observations of linearity at less than 200 mGy are, however, sparse. Some data have been published indicating a non-linear (threshold) response and these are reviewed. In particular one study with X-rays showed a plateau in response up to 50 mGy and with a significant dip below the control level at 4 mGy. The mechanism proposed to explain non-linearity is that low doses stimulate the enzymic repair capability of lymphocytes. Preliminary data are presented from a large experiment by six laboratories in which the low dose-response for X-rays has been re-examined. The plateau in the dose-response relationship, if it exists, does not extend to doses above approximately 10 mGy. No irradiated cells yielded aberration levels significantly below the control. Over the range 0-300 mGy the response can be fitted to a linear regression. There are, however, variations in sensitivity between cells from different donors. An unexpected finding was that some lymphocytes contained greater than 1 exchange aberrations. This may indicate a small subset of cells that are especially susceptible to the induction of aberrations by low doses.     

Evaluation of the risk in autosomal dominant diseases

A lot of traps and difficulties complicate the estimation of a genetic risk in the autosomal dominant diseases. The authors recapitulate the notions of mutation, penetrance and variability and illustrate by some examples the part of each of them, isolated or associated together. The increasing of molecular biology allows to resolve some of these problems, but generate new dangers which are analysed and illustrated.     

Salivary hormones: a new aspect of oral physiology

Aside from the digestive enzymes the submandibular salivary glands (SSG) synthetize other polypeptides, detected also in saliva, with varied biological activity; NGF and EGF are the knowest. However, over the last decade, steroids hormones have been also found out in the saliva at the same concentrations that the free plasma fraction. The origin of these hormones is largely discussed and certain authors have even proposed a local synthesis for them. This matter, is of clinical interest because gingiva and buccal tissues are knowingly sensitive to steroids. Besides, woman ovulation appears to be monitored through progesterone fluctuations in saliva. Another kind of salivary substances is formed by the neuropeptides of the gut-brain axis, mainly VIP and SRIF. The former likely of nervous origin seems to be involved in the atropine-resistant salivary secretion, whereas the latter-likely of SSG origin--appears as a factor associated with glycemia control.     

Thyroid function and trisomy 21. TSH increase and rT3 deficiency

An excess of thyrotropin (TSH) with normal levels of tetraiodothyronine (T4) and of 3,5,3'-triiodothyronine (T3) was confirmed in the serum of 78 trisomy 21 children. A severe deficiency of 3,3',5'-triiodo-thyronine (rT3 or reverse T3) was observed and the decrease of the rT3/TSH ratio was highly significant. These new facts suggest that the rT3 deficiency plays a peculiar role in trisomy 21 (maybe through the regulation of one or few steps of monocarbons' metabolism). A systematic control of thyroid function (including the patient's rT3 level) is mandatory for the follow-up of every trisomy 21 patient.     

Multiple binding of bilirubin to human serum albumin and cobinding with laurate

Numerical analysis of multiple binding of two ligands to one carrier has been accomplished, using the principle of several sets of acceptable binding constants, with bilirubin-laurate-albumin as an example. Binding of bilirubin to defatted human serum albumin was investigated by a spectroscopic method, based upon a difference of light absorption spectrum for free and bound bilirubin. The observations were supplemented with previous data from an independent technique, measurement of oxidation rates of free bilirubin with hydrogen peroxide and peroxidase. A continuous isotherm was obtained, showing binding of at least 4 mol bilirubin per mole albumin with the following stoichiometric binding constants, 1.11 X 10(8), 1.7 X 10(7), 8 X 10(5), and 4 X 10(4) M-1 at pH 8.2, ionic strength 0.15 M, 25 degrees C. The binding is anticooperative at all steps. A saturation level was not reached. Cobinding of bilirubin and laurate was studied, with up to 2 mol of each ligand per mole albumin, using the peroxidase method for determination of free equilibrium concentrations of bilirubin, and a dialysis rate technique for free laurate. The findings could be described in terms of a stoichiometric model. Heterotropic cooperativity was present among the first bilirubin and the first and second laurate molecules. More than two molecules of either ligand can be bound at the same time.     

Characterization, localization, and biosynthesis of acetylcholinesterase in K 562 cells

K 562 cell acetylcholinesterase (AChE), identifiable by active site labeling with radioactive diisopropylfluorophosphate (DFP), showed a Mr around 55,000 in both a crude lysate and a purified sample. The K 562 AChE was reactive with one polyclonal and two monoclonal antibodies produced against human erythrocyte AChE. Subcellular localization, investigated by assay on cell fractions, showed that AChE is membrane bound and that it is located on the cell surface as well as on microsomal and Golgi membranes. Biosynthesis of new enzyme molecules, after inactivation of the constitutive AChE with the irreversible inhibitor DFP, allowed us to follow the kinetics of reappearance in the intracellular compartment and at the cell surface (4 and 8 h, respectively).     

An ATP-dependent Na/Mg countertransport is the only mechanism for Mg extrusion in squid axons

The components of magnesium efflux in squid axons have been studied under internal dialysis and voltage clamp conditions. The present report rules out the existence of an ATP-dependent, Na₀- and Mg₀-independent Mg²⁺ efflux (ATP-dependent Mg²⁺ pump) leaving the Mg²⁺---Na⁺ exchange system as the only mechanism for Mg²⁺ extrusion. The main features of the Mg²⁺ efflux are: (1) The efflux is completely dependent on ATP. (2) The efflux can be activated either by external Na⁺ (forward Mg²⁺---Na⁺ exchange) or external Mg²⁺ (Mg²⁺---Mg²⁺ exchange). (3) The mobility of the Mg²⁺ exchanger in the Na₀⁺-loaded form is greater than that in the Mg²⁺-loaded one. (4) In variance with the Na⁺---Ca²⁺ exchange mechanism, Mg²⁺---Mg²⁺ exchange is not activated by external monovalent cations. (5) ATPγS replaces ATP in activating Mg²⁺---Na⁺ exchange suggesting that a phosphorylation/dephosphorylation process regulates this transport mechanism.     

Periodic cleavage of poly(dA) by oligothymidylates covalently linked to the 1,10-phenanthroline-copper complex

1,10-Phenanthroline (OP) was covalently attached to the 3'-terminus of two oligothymidylates via different linkers [abbreviated as T8-(OP) and T6-(OP)]. In the presence of Cu2+ and 3-mercaptopropionic acid (MPA), these reagents induce a hybridization-dependent cleavage of poly(dA) and of a 27 nucleotide long oligodeoxynucleotide containing an A8 sequence. The principal cleavage sites on the 27-mer span four residues located near the 3'-terminal phosphate group of T8-(OP). When poly(dA) was degraded by T6-(OP) and T8-(OP), a series of bands were obtained corresponding to a repeat unit of six and eight nucleotides, respectively. This periodicity reflects the cooperative binding of oligothymidylate-OP to the polynucleotide matrix and the localized nicking sites.