The load of genetic and partially genetic disease in man. IV. Severe visual handicaps and profound childhood deafness in Hungarian school-age children

In Hungary, the school-age prevalences of severe visual handicaps and of profound childhood deafness have been estimated to be about 6/10⁴ and 10/10⁴, respectively. Most of these conditions have onset at birth or in early childhood and are aetiologically heterogeneous.

Severe visual handicaps are grouped under 11 aetiological categories, their relative contributions to the prevalence being: perinatal damage syndrome (20%; half of this is due to retinopathy of premature infants), cataracts (15%), choroidoretinal degenerations (15%), congenital abnormalities of the eye (15%), syndromes (10%), high myopia ± retinal detachment (7%), postnatal causes (5%), nystagmus (5%), optic atrophy (4%), bilateral retinoblastoma (2%) and prenatal causes (2%). Overall, Mendelian conditions (included under many of the above) account for about 50% with relatively more autosomal dominant than autosomal recessive and sex-linked entities, and acquired causes account for about 40% of the cases studied. No actiology could be assigned in 10% of the cases.

For profound childhood deafness, the rank order of the aetiological categories is: autosomal recessive entities (34%), postnatal causes (22%), perinatal causes (19%), autosomal dominant entities (17%), prenatal causes (5%) and unknown causes (3%).

Severe childhood visual handicaps are responsible for about 60 years of loss of life per 10⁴ live births and about 400 years of impaired life per 10⁴ live births. Genetic causes account for one-quarter of lost life years and three-quarters of impaired life years. The comparable estimates for profound childhood deafness are: about 240 years of life loss per 10⁴ live births (again, about one-quarter due to genetic causes) and about 640 years of impaired life per 10⁴ live births (about one-half due to genetic causes). In all these calculations, it has been assumed that the average life expectancy at birth for an individual in the population is 70 years.     

Phenacetin N-deacetylase and its non-identity with the serotonin sensitive aryl acylamidase of brain

Phenacetin N-deacetylase was characterized in monkey brain. The enzyme needed Triton X-100 for maximal extraction and it had a high specific activity in cerebellum and in the nuclear fraction of whole monkey brain. It differed from the brain aryl acylamidase in both the regional and subcellular distributions. Brain aryl acylamidase purified by affinity chromatography was ineffective in deacetylating phenacetin. All the potent inhibitors of brain aryl acylamidase such as serotonin, tryptamine, acetylcholine and its analogues and neostigmine had no effect on phenacetin deacetylase. However, brain pehnacetin deacetylase was moderately inhibited by indole-3-acetic acid and 5-hydroxy indole-3-acetic acid properties similar to those of liver aryl acylamidase. Acetaminophen was not deacetylated by the brain phenacetin deacetylase.     

The tetraphocomelia -- cleft palate syndrome: description of a new case.

A new case of Tetraphocomelia--cleft palatee syndrome is described. The similiarity between this patient and the cases classified as Pseudothalidomide or as Robert syndrome makes a distinction between these 2 syndromes doubtful.     

Evolution: reducible complexity -- the case for bacterial flagella

A recent paper, which will surely figure centrally in the debate between evolutionists and Intelligent Design creationists, proposes a (perhaps too simple) scheme for the evolution of bacterial flagella.     

Science and representation: the case of genetic maps

At the beginning of the 20th century, the main objective of Mendelian hybridization was, through controlled crosses, to attain the expression of desired "factors", for example in crop improvement. Because of these aims, Mendel's principles were adopted faster among agronomists than academic sectors. The change from the Mendelian conception of factors to the first genetic maps consisted in looking at genes not as abstract and functional entities like in Mendelian studies, but to visualise them as dots on a line, as dots on a map in classical genetics. What genes could do wasn't any more the core interest; their localization on a map was privileged. This new conception was followed by a new way to study, interpret and represent the inheritance phenomena, also, a new way to conduct experiments different from Mendelian hybridization. The construction of the first genetic maps and their representations were a successful means to study, explain and represent different inheritance issues and was a new way in which genetic studies could be done. At the beginning, these maps were hypothetical representations that facilitated the handling of empirical data as well as the classification of mutants. Later on, the culture of mapping strongly contributed to the understanding of the mechanics of chromosomes and the hereditary transmission.     

Molecular mechanism of uncoupling in brown adipose tissue mitochondria. The non-identity of proton and chloride conducting pathways

Specific permeability properties of the inner membrane of brown adipose tissue mitochondria were analysed with the aid of simultaneous pH measurements outside mitochondria and of mitochondria swelling. It was shown that valinomycin-induced potassium diffusion potential drives a parallel passive uptake of chlorides and extrusion of proton. Electrogenic H+ -extrusion was independent on anion transport, no competition was found between the two processes and the former process exerted a lower sensitivity to the inhibitory effect of GDP. The existence of two distinct, independent pathways for translocation of protons and halide anions across the membrane is suggested.     

Native and latent forms of liver phosphorylase phosphatase. The non-identity of native phosphorylase phosphatase and synthase phosphatase.

The directly measurable (native) phosphorylase phosphatase present in a fresh mouse liver extract is bound to particulate glycogen and is not inhibited by heat-stable inhibitors. Treatment of the extract with trypsin or ethanol at room temperature caused a more than 10-fold increase in phosphorylase phosphatase activity. This increased activity stems from the activation of completely inactive (latent) enzyme, the major part of which is present in the high-speed supernatant. The trypsin-revealed activity can be completely blocked by heat-stable inhibitors. Treatment of the animal with glucocorticoids increases, and fasting decreases the activity of the native phosphorylase phosphatase. The level of latent enzyme, however, is unaffected by these treatments. The major portion of synthase phosphatase in the fresh liver extract is bound to glycogen. This enzyme is inhibited by the heat-stable inhibitor-2 and inactivated by trypsin or ethanol as well as by several treatments that have little effect on phosphorylase phosphatase. Upon DEAE-cellulose chromatography at 0 degrees C of a fresh liver extract, phosphorylase phosphatase and synthase phosphatase were resolved as separate, single peaks. If the preparation was not kept at 0 degrees C during the entire procedure, two peaks of each enzyme were observed. Under these conditions the first peak of phosphorylase phosphatase and of synthase phosphatase coincided. From these findings it is concluded that synthase phosphatase and phosphorylase phosphatase, in their native form, are distinct enzymes.