Entwicklung der Zähne

Dental development takes place in stages over a long period of time. From the 6ths embryonal week, when the dental lamina develops, tooth number and shape are formed, followed by the production of dental hard tissues. Genetic dental developmental defects are not rare. Mostly these defects affect the tooth number, predominantly resulting in a decrease tooth number (hypodontia) which can occur isolated or as a finding in genetic syndromes such as Rieger syndrome, Witkop syndrome or several ectodermal dysplasias. Genetic defects of dental hard tissues are less frequent, different types of isolated enamel defects (amelogenesis imperfecta) are known. Dentinogenesis imperfecta or other dentinal defects are either caused by different mutations of the DSPP gene or a part of osteogenesis imperfecta.     

Unchanged levels of interleukins, neopterin, interferon-gamma and tumor necrosis factor-alpha in cerebrospinal fluid of patients with dementia of the Alzheimer type.

Several histopathological studies suggest that amyloidogenesis in dementia of the Alzheimer type is accompanied by activated glia and glia-derived cytokines, leading to chronic, self-propagating, cytokine-mediated molecular and cellular reactions. As studies regarding inflammatory changes in cerebrospinal fluid of patients with dementia of the Alzheimer type has been inconclusive, we set up a prospective study to assess cerebrospinal fluid levels of interleukin-1beta, interleukin-6, interleukin-10, interleukin-12, soluble interleukin-2 receptor, interferon-gamma, tumor necrosis factor-alpha and neopterin in 20 patients with dementia of the Alzheimer type and 20 age- and sex-matched controls. Comparing both groups, no significant differences in concentrations and specific activities could be revealed. An additional 22 patients were included to enlarge the study population. No statistically significant differences were shown comparing patients (n=42) with the control group (n=20). We conclude that the immune-mediated inflammatory changes found in histopathological studies are not reflected in cerebrospinal fluid of patients with dementia of the Alzheimer type. Probably, cytokine production appears very localized in the central nervous system, not allowing representative detection in cerebrospinal fluid. Further studies assessing cytokine levels in various regions of central nervous system of patients with dementia of the Alzheimer type will be of interest to confirm this hypothesis.     

Das Marfan-Syndrom und verwandte monogene Krankheiten der Aorta

Marfan syndrome (MFS) is an autosomal dominant, pleiotropic disease of the connective tissue with a prevalence of about 1 in 5000 persons. MFS is characterized by manifestations in the cardiovascular system, eye, skeleton, lung, skin, and dura mater that show a high degree of intra- and interfamilial variability. Many manifestations develop during or shortly before puberty; severe complications rarely occur before adulthood. Many patients with MFS display a so-called marfanoid habitus with tall stature, dolichostenomelia (long, narrow extremities), dolichocephaly (disproportionately long and narrow head), as well as other skeletal abnormalities such as scoliosis and pes planus. Scoliosis occurs in approximately 60% of those affected, pectus deformities in up to two thirds. Ectopia lentis is seen in many patients with MFS and is almost always bilateral. MFS is characterized by a high risk for complications such as severe scoliosis or pectus deformities, spontaneous pneumothorax, retinal detachment, or glaucoma secondary to lens luxation. The most severe complications occur in the cardiovascular system, including in particular acute dissection of the ascending aorta, which generally follows a long period of progressive aortic dilatation. Before the introduction of modern treatment modalities, the average life expectancy of persons with MFS was estimated to be 32 years. Today, with medical care in multidisciplinary centers, an average life expectancy of over 60 years can be achieved. This article offers a review of established and novel concepts for the diagnosis and treatment of MFS and other hereditary diseases of the aorta.     

Structure of the specific combining ability between two species of Eucalyptus.II. A clustering approach and a multiplicative model

The Eucalyptus breeding program of URPPI (a partnership between CIRAD-Forêt, Centre National de la Recherche Forestière du Congo, and Unité d’Aforestation Industrielle du Congo) consists of a reciprocal recurrent selection scheme developed in the Congo between the two species Eucalyptus urophylla and Eucalyptus grandis. Two approaches are proposed in order to model and predict the specific combining ability (SCA) between these species. The clustering approach uses a simultaneous clustering procedure of the two species based on SCA and reveals heterotic groups coherent with the geographical origins of E. urophylla genotypes. The second approach uses a multiplicative model to partition the SCA into three multiplicative terms explaining 95% of the interaction.     

Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose.

Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones.     

Klinik und Genetik des familiären Darmkrebses

Familial clustering of colorectal cancer (CRC) and early disease onset are indicators of an inherited tumour syndrome. Monogenic dispositions account for 3–5% of all CRC cases and are subdivided into hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome) and various gastrointestinal polyposis syndromes. Many of these syndromes are characterised by a broad spectrum of extracolonic tumours. Early detection and accurate classification are essential in providing effective surveillance and treatment. Initial diagnosis is based on endoscopic and histological findings as well as on the presence of extracolonic manifestations and family history. Molecular genetic examination is important for the differential diagnosis, evaluation of recurrence risk, and predictive testing of asymptomatic at risk individuals; it is performed according to largely standardised algorithms. Diagnostic difficulties are common among the hamartomatous polyposes due to their broad phenotypic overlap and frequent uncertainties in histological evaluation, as well as among patients with few adenomas. Risk-adapted surveillance guidelines have been established for HNPCC and for the more frequently observed polyposis syndromes. Beyond established tumour syndromes, familial clustering of CRC (which is often of late onset) or the occurrence of few adenomas is likely to be based upon a multifactorial (complex) etiology. Although identification of the underlying genetic risk factors and biological pathways is still in the early stages, rapid progress is being made due to methodical developments such as genome-wide association studies and CNV analysis.     

TNF-alpha-treated DC exacerbates disease in a murine tumor metastasis model

Due to the pivotal role that dendritic cells (DC) play in eliciting functional anti-tumor T cell responses, immunotherapeutic approaches utilizing DC-based vaccines have readily been exploited. It has been argued that, in the setting of immunotherapy, mature DC will be more efficient at T cell priming and, therefore, required for effective vaccination. As TNF-alpha is commonly used as a DC maturation factor, we have examined the efficacy of treatment with DC matured with TNF-alpha (DC-TNF) in a murine model of melanoma. We have now shown that treatment with DC-TNF leads to an increase in the number of lung metastases as compared to mice treated with immature DC. No differences in the number of CD4⁺CD25⁺ T-regulatory cells were measured in the lungs of DC-TNF-treated mice. On examination of the infiltrating lymphocytes, an enhanced secretion of IL-10 and a higher percentage of CD4⁺IL-10⁺ T cells were measured in the lungs of DC-TNF-treated mice. However, treatment with DC-TNF did not enhance the number of melanoma lesions in the lungs of IL-10 knockout mice or in mice depleted of CD4⁺ T cells. Together, these studies indicate that treatment of melanoma-bearing mice with DC treated with TNF-alpha can induce IL-10 production by resident cells at the tumor site, leading to immune tolerance and exacerbation of disease.     

What is the genetic origin of teak (<Emphasis Type="Italic">Tectona grandis</Emphasis> L.) introduced in Africa and in Indonesia?

The first introduction of Tectona grandis in Indonesia took place between the fourteenth and sixteenth centuries and in Africa in the nineteenth century. A total of 1.1 and 0.3 million ha, respectively were planted in the two areas. The extension of teak plantations often started from these first introductions. Unfortunately, the documentation concerning dates, planting stocks and the sources of origin of the teak imported into the different countries was very inaccurate. In this study, the use of 15 microsatellite molecular markers enabled us to compare 22 exotic teak provenances with 17 provenances of the natural range. Results of the analysis showed that the provenances from South India were not related to the provenances that were first introduced in either Africa or Indonesia. Nearly 95% of teak landraces in Benin, Cameroon, Côte d’Ivoire, Tanzania, Togo and Senegal came from North India, and 96% of Indonesian and Ghanaian teak appeared to be very closely linked to Central Laos. The genetic origin of introduced teak was confirmed by the main traits of interest of provenances observed in international trials. Thus, trees from North India had very bad stem forms compared to Laotian and Thai provenances, which generally had good stem forms but low vigour. This genetic knowledge is essential for programmes to develop varieties and to improve the quality of plantations, particularly in Africa.     

Phylogeography of Eastern Polynesian sandalwood (Santalum insulare), an endangered tree species from the Pacific: a study based on chloroplast microsatellites

Aim Patterns of genetic variation within forest species are poorly documented in island ecosystems. The distribution of molecular variation for Santalum insulare, an endangered tree species endemic to the islands of eastern Polynesia, was analysed using chloroplast microsatellite markers. The aims were to quantify the genetic diversity; to assess the genetic structure; and to analyse the geographical distribution of the diversity within and between archipelagoes. The ultimate goal was to pre‐define evolutionary significant units (ESUs) for conservation and restoration programmes of this species, which constitutes a natural resource on small, isolated islands. Location Eleven populations, each representative of one island, covering most of the natural occurrence of S. insulare were sampled: five populations from the Marquesas Archipelago; three from the Society Archipelago; and three from the Cook–Austral Archipelago. These South Pacific islands are known for their high degree of plant endemism, and for their human occupation by Polynesian migrations. The extensive exploitation of sandalwood by Europeans nearly 200 years ago for its fragrant heartwood, used overseas in incense, carving and essential oil production for perfume, has dramatically reduced the population size of this species. Methods We used chloroplast microsatellites, which provide useful information in phylogeographical forest tree analyses. They are maternally inherited in most angiosperms and present high polymorphism. Among the 499 individuals sampled, 345 were genotyped successfully. Classical models of population genetics were used to assess diversity parameters and phylogenetic relationships between populations. Results Four microsatellite primers showed 16 alleles and their combinations provided 17 chlorotypes, of which four exhibited a frequency > 10% in the total population. The gene diversity index was high for the total population (H_e = 0.82) and varied among archipelagoes from H_e = 0.40 to 0.67. Genetic structure is characterized by high levels of differentiation between archipelagoes (36% of total variation) and between islands, but differentiation between islands varied according to archipelago. The relationship between genetic and geographical distance confirms the low gene flow between archipelagoes. The minimum spanning tree of chlorotypes exhibits three clusters corresponding to the geographical distribution in the three main archipelagoes. Main conclusions The high level of diversity within the species was explained by an ancient presence on and around the hotspot traces currently occupied by young islands. Diversity in the species has enabled survival in a range of habitats. Relationships between islands show that the Cook–Austral chlorotype cluster constitutes a link between the Marquesas and the Society Islands. This can be explained by the evolution of the island systems over millions of years, and extinction of intermediary populations on the Tuamotu Islands following subsidence there. Based on the unrooted neighbour‐joining tree and on the genetic structure, we propose four ESUs to guide the conservation and population restoration of Polynesian Sandalwood: the Society Archipelago; the Marquesas Archipelago; Raivavae Island; and Rapa Island.     

Possible preadaptations to speech. A preliminary comparative

Human language is a unique phenomenon and its evolutionary origins are uncertain. In this paper we attempt to explore some of the preadaptations that might have contributed to the origin of human speech. The comparative approach we use is based on the assumption that all features of a species are functional, and that all features can be compared with those of other animals and correlated with certain lifestyles. Using this method we attempt to reconstruct the different evolutionary pathways of humans and chimpanzees after they split from a common ancestor. Previous results from comparative studies suggest human ancestors may not have evolved on the open African savannas as was once believed, but more probably were coastal omnivores feeding on plant matter and easy to catch invertebrates such as shellfish from beaches and shallow waters. Fossil and archaeological data suggest this coastal phase occurred at the beginning of the Pleistocene, whenHomo ergaster-erectus dispersed between East-Africa, North-Africa, South-Asia and Indonesia. This paper presents comparative data suggesting the various human speech skills may have had their origins at different times and may originally have had different functions. Possible preadaptations to speech include, for instance, musical skills present in a variety of primate species (sound production); airway closure and breath-hold diving for collecting seafood (voluntary breath control); and suction feeding adaptations for the consumption of fruit juice or certain seafoods (fine control of oropharyngeal movements). The different evolutionary pathways of chimpanzees and humans might explain why chimpanzees lack language skills and why human language is a relatively recent phenomenon.