Smoking and poverty.

The problem of poverty leads to increased use of both legal and illegal drugs. Tobacco and alcohol are legal drugs that cause particular concern. Both drugs are widely abused in Germany by people attempting to escape their everyday problems. For decades it has been known that tobacco and alcohol use are more prevalent in lower socio-economic groups of society (those with low educational achievement, compared with people with further or higher education qualifications). Tobacco and alcohol use is particularly high among the unemployed, either temporarily or long-term, as well as people living alone. Children and women are more concerned about smoking than men. Female loneliness, often accompanied by the appearance of depressive reactions or of depression, increases the likelihood of cigarette smoking. Poor people spend up to 20% of their income on tobacco. In many industrialized countries, the age of onset of smoking is becoming younger and younger, increasing the risk of development of avoidable tobacco-related illnesses at an earlier age. This means that young smokers who develop chronic tobacco-related illnesses will require medical care over many years, increasing the cost of treating tobacco-related disease. Within the next few years, effective prevention programs against smoking must be developed, particularly for the lower socio-economic populations, in order to stop the cost of healthcare systems spiraling over the coming decades.     

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities.     

A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations

Plectin is one of the largest and most versatile cytolinker proteins known. In basal keratinocytes it links the intermediate filament network to cell membrane-associated hemidesmosomes. Several mutations in its gene have been identified that lead to the recessive disease epidermolysis bullosa with muscular dystrophy. We report here a mutation that leads to a dominant form of the disease, epidermolysis bullosa simplex Ogna. We found that the epidermolysis bullosa simplex Ogna phenotype is due to a site-specific missense mutation within plectin's rod domain. Further, we show that epidermolysis bullosa simplex Ogna is not restricted to a single Norwegian kindred as previously believed. A German family with the phenotypic hallmarks of epidermolysis bullosa simplex Ogna was found to carry an identical de novo mutation. These two mutations arose about 200 y apart in time. Consistent with the absence of muscular symptoms in these patients, muscle biopsies from several epidermolysis bullosa simplex Ogna members of the Norwegian kindred showed normal staining patterns using antibodies to plectin. Skin changes in epidermolysis bullosa simplex Ogna patients are documented on the ultrastructural level.     

Multiple lentigines (LEOPARD) syndrome. Case reports and review of the literature

The rarely occurring multiple lentigines (LEOPARD) syndrome represents a complex of skin, heart, skeleton and other malformations and is described in a 36-year-old male and his 9-year-old daughter. With the occurrence of multiple lentigines, the diagnostic search for further malformations should always be undertaken. Its differential diagnosis and its pathogenetic and clinical aspects are discussed in this paper.     

Die individuelle Rezeptur in der spezifischen Immuntherapie Notwendigkeit und Fehlerquellen

The causal treatment of type I allergies by specific immunotherapy (SIT) is absolutely essential to counter the transformation of rhinitis into bronchial asthma. There are therapy allergens available for this purpose as finished drugs (with marketing authorization and subject to official batch testing) or as named patient products (NPP). Sixty to eighty percent of all preparations for SIT are compounded as NPP for a specific patient by his physician. Because of the enormous number of potential allergens, SIT also requires NPP, as the batchwise production of finished drugs would not be practical for possibly very small groups of patients. However, NPP may become a source of error in treating allergic diseases due to the compilation of mixtures for therapy being attributed to an inadequate anamnesis obtained through physicians without allergological experience, the compilation of mixtures of non cross-reacting allergens that may negatively influence the stability and efficacy of such a mixture, up to total ineffectiveness by proteolytic degradation, and the failure to reach the concentration essential for a clinical effect of each single allergen in a mixture. All these factors can only be controlled by intensive training of practising allergists and their cooperation with responsible acting manufacturers, since up till now efforts to subject NPP to binding regulations, comparable to those existing for preparations with marketing authorization, have failed.