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Das Prostatakarzinom ist eine heterogene Erkrankung. Im Falle eines Niedrigrisikokarzinoms stellt die aktive Überwachung eine attraktive Therapiealternative dar. Einschneidende Komplikationen einer definitiven Therapie können somit aufgeschoben bzw. ganz vermieden werden. Trotz strenger Einschlusskriterien für die aktive Überwachung ist die Diagnose eines Niedrigrisikokarzinoms aber nicht immer korrekt gestellt. Es verbleibt ein Risiko, dass der optimale Zeitpunkt einer definitiven Therapie verpasst wird. Eine multimodale Diagnostik sowie eine engmaschige Nachsorge sind deswegen essenziell.

BACKGROUND: A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified. METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology. CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.

To investigate anticipation in proximal myotonic myopathy (PROMM).

Two carriers of a balanced translocation, one paternal t(9q-;13p+) and one maternal t(3q-;15p+), were studied cytogenetically with selective silver staining to localize more precisely the break points on the short arms of the two acrocentric chromosomes involved. The distal ends of both chromosomes 3 and 9 reacted positively to the selective silver staining. This observation allows the conclusion that the NOR (nucleolar organizer region), or parts of it, is in fact active in organizing nucleoli and by implication produces rRNA after the translocation onto chromosomes 3 and 9.

Fabry's disease (angiokeratoma corporis diffusum) can be diagnosed by determination of a-galactosidase activity in single hair roots. A technique has been developed permitting subsequent analysis of enzyme activity and protein content of hair root cells. We have applied this method examining 8 obligatorily heterozygous sisters as well as their 5 daughters and 10 sons. Especially for identification of heterozygotes, the method described proved to be easy and reliable.

Three families with X-linked lymphoproliferative disease were studied. Affected males clinically presented with severe or fatal infectious mononucleosis, acquired hypogammaglobulinaemia, hypergammaglobulinaemia M, and malignant lymphoma including Hodgkin disease. Haplotype analysis using various DNA markers from Xq25-q27 allowed the prediction of the carrier status in females and identification of the XLP status in asymptomatic males.

The discriminatory power of a quantitative heterozygote test for Maple Syrup Urine Disease (MSUD) which we have been using is analyzed on the presumption that a single rare mutant allele is involved in MSUD. Bayes theorem then predicts that only a small portion of persons from the general population with activities in the heterozygous range really are heterozygotes.

This paper outlines a fast and simple GC technique for on-line analysis of the products of hydrodenitrogenation of pyridine. Two separate columns, viz., Carbowax 1500/Chromosorb W, and n-Octane/Porasil C, which are sequenced with a 10-port sampling valve are used for this purpose. The 10-port valve is maneuvered so as to accomplish the separation of C1-C5 paraffins, C3-C5 olefins and pyridines in a single injection of sample.

Alkaptonuria (AKU; McKusick no. 203500) is a rare autosomal recessive disorder caused by the lack of homogentisic acid oxidase activity. Patients excrete large amounts of homogentisic acid in their urine and a black ochronotic pigment is deposited in their cartilage and collagenous tissues. Ochronosis is the predominant clinical complication of the disease leading to ochronotic arthropathy, dark urine, pigment changes of the skin, and other clinical features. A mutation causing alkaptonuria in the mouse has mapped to chromosome 16. Considering conserved synteny, we were able to map the human gene to chromosome 3q in six alkaptonuria pedigrees of Slovak origin.

The characteristics of carcinoembryonic antigen (CEA) molecules expressed by different cell types have been examined using cDNA transfection into cells of epithelial, neuroectodermal and hematopoetic origin. Variability in the CEA molecules was observed in terms of monoclonal antibody binding, apparent molecular weight and sialic acid content, although this was not cell type specific. CEA was found to mediate homotypic as well as heterotypic intercellular adhesion independently of the cell type and despite differences in the sialic acid content. Although CEA was shown to function as a homophilic cell adhesion molecule in most cells, expression of CEA in one cell line led to a reduction in both homotypic and heterotypic cell adhesion, suggesting that it can under certain circumstances also function as a repulsion molecule.

The extended Kantorovich method is used to obtain solutions for a large number of previously unsolved elastic buckling problems of thin rectangular plates. In the present work, this method is specially adapted to a numerical method of solution. Verification of the solution method is made by solving a large number of plate buckling problems with known classical solutions. Included among the new problems solved are plates with a variety of boundary conditions, plates on elastic foundations, and plates with a variable inplane compressive load applied to only one edge, together with several different in-plane prestress configurations to increase the magnitude of the critical stress.

Van der Woude syndrome (VWS) is an autosomal dominant disorder associated with one or more of the following features: clefting of the primary or secondary palate, hypodontia or lower lip pits. It has been estimated to account for 2% of all cases of cleft lip and palate. VWS is one of the rare disorders in which clefting of the primary and secondary palate may be seen to segregate as components associated with the same gene. Because of its autosomal dominant inheritance, VWS is readily accessable to linkage analysis as a preliminary step in the identification of the molecular abnormality underlying the clefting effect in the primary and secondary palate. A reported linkage between REN and VWS has promoted us to use pHRnX3.6 (REN) and several markers surrounding REN for a linkage analysis in a large Swiss family. In a second step, linkage analysis was performed to study restriction fragment length polymorphisms for the candidate gene TGFB2 and other loci recently mapped to the candidate region 1q32–1q41. Evidence for linkage (? = 0.00, lod score = 3.01) between REN and VWS could be confirmed in this pedigree. TGFB2 demonstrated recombination with the disease locus and is unlikely to be causative in VWS. The results of a multipoint linkage analysis showed that VWS was flanked by D1S65 and TGFB2 at a maximum location score of 20.3.

Gives advice on wintertime photography. Under exposure and how to prevent it; How to protect a camera and lens from snow and cold; Kodak Weekend 35 waterproof camera; Condensation problems; How to photograph winter sunshine and shadows.

Discusses eight-millimeter, or miniature, camcorders. 8mm videocassettes; Hi-Band 8mm camcorders; Controls; Features, such as an edit/search button, variable shutter speeds, power zoom lenses; Tripods.

A linkage analysis with 12 DNA markers from proximal 19q was performed in eight families with central core disease (CCO). Two-point analysis gave a peak lod score of Z = 4.95 at θ = 0.00 for the anonymous marker D19S190 and of Z = 2.53 at θ = 0.00 for the ryanodine receptor (RYR1) candidate gene. Multipoint linkage data place the CCO locus at 19q13.1, flanked proximally by D19S191/D19S28 and distally by D19S47. This map location includes the RYR1 gene. The results of the linkage study present no evidence for genetic heterogeneity of CCO. Copyright 1993, 1999 Academic Press

We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Müller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy.

Summary A case report of a de novo deletion in the short arm of chromosome 7 is presented (46,XX,del(7)(p21→pter)). The five-month-old girl's major symptoms are: trigonocephalus with craniosynostosis, median bony forehead bulge, high palate, atrial septal defect, anal atresia and perineal fistula, thumb insertion far to ulnar-proximal, and a slightly retarded psychomotor development. The other cases with monosomy 7p described in the literature are reviewed.

A novel procedure is presented to estimate the ratio of male to female mutation rates for Duchenne muscular dystrophy (DMD). X-specific restriction fragment length polymorphisms are used to establish DNA haplotypes in three-generation DMD families. From the proportion of DMD patients who have inherited their maternal grandfather's X chromosome, the ratio of mutation rates can be calculated. In contrast to classical methods, the proposed procedure is not restricted to sporadic or familiar cases nor is any information on the carrier status of female relatives required.

Explains how to select a photographic tour. Names photography magazines and directories. Gives names of several professional photographers and the tours they lead.

alpha 1‐acid glycoprotein (AAG) concentration and the binding of both lignocaine and warfarin were compared in 15 healthy Chinese and age and sex matched Irish (Caucasian) subjects. Both the extent of lignocaine binding and AAG concentrations were significantly (P less than 0.05) lower in Chinese subjects. No difference was shown in warfarin binding. These results suggest that the binding of basic drugs may be significantly less in Chinese than Caucasians, and lower concentrations of the binding protein AAG are a major determinant of this difference.

ALTHOUGH many unfertilised mouse oocytes have been variously stimulated to develop into embryos—parthenogenones—all have died soon after implantation1. The suggested causes of this failure include homozygosity of recessive lethals and an incomplete cortical reaction1. It is not known whether the lack of the paternally-derived genome inhibits their proper development. Using selective silver staining2,3we have examined the activity of the genes for 18S and 28S ribosomal RNA during preimplantation development of parthenogenones. From studies of the activity of nucleolus organisers on the chromosomes of human–mouse cell hybrids, it has been assumed that silver precipitation was a consequence of gene activity for 18S and 28S rRNA (refs 4–6). Our results indicate that these genes are activated during early embryogenesis and without the need for paternally-derived factors.

The X-linked recessive centronuclear myopathy (XLR-CNM), a severe neonatal disorder characterized by generalised hypotonia, muscle weakness and primary asphyxia, has recently been mapped to Xq28. We investigated 70 members of eight CNM-families using the Xq28 probes DX13, St14, FVIII, 767, and cpX67 Strong linkage was found with St14 (lod score z = 3.12 ; T = 0.01), followed by FVIII, DX13, and 767, proving them to be useful for prenatal diagnosis (pnD). This is the first report on pnD in two CNM-families: In family 1 two pnD have been performed for an obligate carrier having had two affected sons. Linkage analyses using probes DX13, Stl4, and 767 showed a male fetus having inherited the same X-chromosome as his two deceased brothers, and the parents choose abortion. In a further pregnancy the fetus was a girl having no risk of being affected. The patient of family 2 was a sporadic case and the mother's carrier state was not known. PnD in the second pregnancy detected that the fetus had inherited the grandpatemal X-chromosome as his deceased brother. At birth the boy was affected, proving that pnD was correct and that the CNM-mutation had occured during the grandpatemal spermiogenesis. This presentation points to the fact, that in families at risk for CNM pnD can now be offered.