Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familial and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia.

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Inhibition of T-antigen-binding cells by idiotypic antisera.

Shared idiotypy between B- and T-cell receptors specific for the antigen L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was studied in an antigen-binding assay using idiotypic antisera. These idiotypic reagents were prepared by inoculation of rabbits with purified anti-tyr(TMA) antibody raised in strain 13 guinea pigs. The antisera blocked 78-83% of the antigen-binding T cells (T-ABC) and 50-55% of the antigen-binding B cells (B-ABC) from tyr(TMA)-immune strain 13 and outbred lymph node cells (LNC). An excess of normal guinea pig Ig in the ABC assay did not affect the ability of the idiotypic antisera to block T- and B-ABC. Nylon wool-passed tyr(TMA)-immune LNC were trypsin treated resulting in a 75% loss of T-ABC. The trypsin-treated population was then cultured for 16 h which resulted in a return of T-ABC to 92% of pretrypsin values. 77% of these regenerated T-ABC could be blocked with idiotypic antisera. Specificity of the idiotypic antisera was tested in L-tyrosine-p-azobenzenearsonate-immune guinea pig LNC. Neither T- nor B-ABC were blocked in this heterologous system. Further blocking experiments were performed to characterize the nature of the T-ABC receptor. A variety of anti-Ig reagents, some of which block B-ABC, do not inhibit T-ABC suggesting that variable regions on T cells are not linked to Ig Constant regions.

A public database for gene expression in human cancers.

A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE) the user can compare transcript populations between any of the posted libraries. As an initial demonstration of the database's utility, gene expression in human glioblastomas was compared with that of normal brain white matter. Of the 47,174 unique transcripts expressed in these two tissues, 471 (1.0%) were differentially expressed by more than 5-fold (P<0.001). Classification of these genes revealed functions consistent with the biological properties of glioblastomas, in particular: angiogenesis, transcription, and cell cycle related genes.

Characterization of the human neurocan gene, CSPG3.

Neurocan is a chondroitin sulfate proteoglycan thought to be involved in the modulation of cell adhesion and migration. Its sequence has been determined previously in rat and mouse (Rauch et al., 1992. Cloning and primary structure of neurocan, a developmentally regulated, aggregating, chondroitin sulfate proteoglycan of the brain. J. Biol. Chem. 267, 19536-19547; Rauch et al., 1995. Structure and chromosomal location of the mouse neurocan gene. Genomics 28, 405-410). We describe here the complete coding sequence of the human neurocan mRNA, known as CSPG3, as well as mapping data, expression analysis, and genomic structure. A cDNA known as CP-1 was initially sequenced as part of a gene discovery project focused on characterizing chromosome 19-specific cDNAs. Sequence homology searches indicated close homology to the mouse and rat proteoglycan, neurocan (GenBank accession Nos X84727 and M97161). Northern analysis identified a brain-specific transcript of approx. 7.5kb. A longer cDNA clone, GT-5, was obtained, fine-mapped to the physical map of chromosome 19 by hybridization to a chromosome-specific cosmid library, and sequenced. Full coding sequence of the mRNA indicates a 3963bp open reading frame corresponding to a 1321 amino acid protein, similar to the protein length found in mouse and rat. The amino acid sequence of human neurocan shows 63% identity with both the mouse and rat sequences. Finally, genomic sequencing of a cosmid containing the complete neurocan gene was performed to determine the genomic structure of the gene, which spans approx. 41kb, and is transcribed in the telomere to centromere orientation.

Expression of multiple larger-sized transcripts for several genes in oligodendrogliomas: potential markers for glioma subtype.

Astrocytomas and oligodendrogliomas are two brain tumors that follow different clinical courses. Although many of these tumors can be identified based on standard histopathological criteria, a significant percentage present notable problems in diagnosis. To identify markers that might prove useful in distinguishing glioma subtypes, we prepared and analyzed cDNA libraries for differential expression of genes in an astrocytoma (grade II), an oligodendroglioma (grade II), and a meningioma (benign). The tumor libraries were compared by sequencing randomly selected clones and tabulating the expression frequency of each gene. In addition to identifying several genes previously reported or expected to be differentially expressed among these tumors, several potential new brain tumor markers were identified and confirmed by Northern blot analysis of a panel of brain tumors. A surprising result of this analysis was the observation that several larger-sized transcripts for various genes were predominantly expressed in the oligodendroglioma tumors, when compared to the other brain tumors or in non-tumor gray matter. These findings are consistent with different pre-mRNA splicing patterns observed between oligodendrogliomas and astrocytomas. In support of this hypothesis, our screen revealed significantly higher levels of two hnRNP A1 transcripts in oligodendrogliomas. hnRNP A1 is a component of the spliceosome whose expression levels affect splice site selection in vivo. The preferential expression of larger-sized transcripts for several genes in oligodendrogliomas may be useful for distinguishing astrocytic and oligodendroglial gliomas.

[Available methods to modify primary graft rejection (author's transl)]. / Möglichkeiten zur Beeinflussung der primären Transplantatabstossung.

Primary graft rejection is an immunological reaction. Many modes of preventing, or at least, delaying rejection have already been tested. The present study deals with experiences and possible mechanisms of action of nonspecific immunosuppression caused by different drugs or antilymphocytic sera; furthermore, an account is given of the latest stand of knowledge gained from experimental studies to induce immunological enhancement, as well as immunological tolerance to transplantation antigens.

[Injuries in occupational accidents]. / Verletzungen bei Arbeitsunfällen.

Evaluation of 3,096 accidents occurred during occupational activity in industry reveals the following results: most of the injuries of men are more serious than these of women. Ranking the injured parts of the body shows that injuries of the hand are most frequent. Moreover ranking the injured parts of the body as well as the nature of injuries reveals that there are notable differences between the two sexes.

[Immunobiological fundamentals of primary graft rejection (author's transl)]. / Immunbiologische Grundlagen der primären Transplantatabstossung.

Graft rejection caused by genetic differences between donor and recipient is an immunological reaction of transplantation antigens with mechanisms of primarily cellular immunity, and later on even of humoral immunity. For initiating the immune response of the recipient three stages have to be distinguished: 1. Recognition of determinant groups of transplantation antigens by menbrame receptors at the surface of immunologically competent lymphocytes. 2. Differentiation and proliferation of immunologically activated lymphoid cells into cellular antibodies and plasma cells, the receptor molecules of which could be identified as immunoglobulins and which are sent into the blood as circulating humoral antibodies, , partially as complement fixing ones. 3. Effector phase, in the course of which the lysis of the graft is caused by target cell destruction. Many problems still remain unsolved, but now as ever, the basis of most experimental studies is still formed by Burnet's clonal selection theory.

[Accident and injuries situations in accidents at school and on the way to and from school]. / Das Unfall- und Verletzungsgeschehen bei Schulunfällen und Schulwegeunfällen.

In the Federal Republic of Germany, where accidents to schoolchildren are covered by the statutory accident insurance, a total of 991,947 accidents of this kind occurred in 1987, 133 of which were fatal. In this study, the accidents and injuries sustained by 1059 schoolboys and schoolgirls who received medical treatment in our clinics are analysed. We are concerned here with 887 accidents actually at school and 172 accidents on the way to or from school. In the case of accidents at school, the proportion of 6-, 7- and 8-year-olds affected was below 3% for each of these age groups. The percentage of children involved in accidents at school increased steeply with increasing age, reaching a peak in girls at 12 years of age, with 15.4%, and in boys at 13 years, with 14.5%. After this, the proportion in each individual age group lay between 10% and 12% up to 17 years of age and decreased to 7% in 19-year-olds. The proportion of accidents among 20- and 21-year-olds was less than 2%. Of the 887 accidents at school, 53% occurred during sports lessons, 28% during break times, 11% in the course of the general coming and going involved in attendance on the school premises, 3% during instruction in academic subjects and 3% during extracurricular activities, e.g. school outings. Each of these accident areas has its typical accident risks, and often its characteristic accident pattern in addition. Furthermore, there are age-specific and sex-specific features. The frequency of injuries to the upper extremities, including the hand, was 11% higher in girls than in boys.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thoracic injuries in traffic accidents and non-traffic accidents]. / Thoraxverletzungen bei Verkehrsunfällen und Nichtverkehrsunfällen.

Traffic accidents differ from non-traffic accidents where the injuries are concerned. With the males two thirds of the thoracic injuries happened in non-traffic accidents and one third in road accidents; with the females, the relation was reversed. In thirteen per cent of the traffic accidents and in twenty-five per cent of the non-traffic accidents there were only thoracic injuries, in the other cases there were multiple injuries. Blunt damages of the thorax occurred in the majority of both kinds of accidents, penetrating injuries were less common. Closed rib fractures happened twice as often in traffic accidents as in accidents at work. Compound fractures of the ribs were three times as frequent in non-traffic accidents as in traffic accidents. In thirty-five per cent of road accidents and in twenty-two per cent of non-traffic accidents the injuries were of an intrathoracal kind. Of all the three hundred and thirty thorax injured patients thirty-four did not survive their injuries, twenty-nine due to traffic accidents, and five due to non-traffic accidents.