RESUMO
OBJECTIVE: To establish genetic linkage between polymorphic microsatellite loci and a disease locus responsible for an autosomal recessive type of nonsyndromic mental retardation (MR). BACKGROUND: Although MR is the most common developmental disability in the United States, the etiologies of most nonsyndromic cases are not known. METHODS: A genealogic database provided information to reconstruct the relationships between 32 individuals from five nuclear families in a single pedigree with 10 affected individuals with nonsyndromic MR. To find a MR disease locus in this population, we performed a genome-wide search using genetic loci spaced at 10- to 20-cM intervals. Pairwise linkage analysis, multipoint linkage analysis, and haplotype reconstruction were used to localize the disease gene. RESULTS: Genetic linkage between a MR disease locus and locus D3S3050 on chromosome 3p25-pter was established with a Zmax = 9.18 at theta = 0.00. Fine mapping this region delimited a 13. 47-cM candidate interval defined by key recombinants at loci D3S3525 and D3S1304. Multipoint linkage analysis refined the critical region to a 6.71-cM interval flanked by loci D3S3525 and D3S1560. Evidence that a gene for MR resides in this location is supported by previous breakpoint deletion mapping studies performed in the chromosome 3p- syndrome. CONCLUSIONS: These results suggest that a gene on the subtelomeric region of chromosome 3p contributes to general intelligence. The genes for the cell adhesion L1-like molecule (CALL), the inositol triphosphate receptor (ITPR1), and the AD neuronal thread protein (AD7c-NTP) are leading positional candidates because of their role in brain development, neuronal signaling, and structure.
Assuntos
Cromossomos Humanos Par 3 , Ligação Genética , Deficiência Intelectual/genética , Mutação , Proteínas do Tecido Nervoso , Adulto , Canais de Cálcio/genética , Proteínas de Ligação ao Cálcio/genética , Criança , Mapeamento Cromossômico , DNA Satélite/análise , Saúde da Família , Feminino , Genótipo , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Complexo Antígeno L1 Leucocitário , Litostatina , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Moléculas de Adesão de Célula Nervosa/genética , Linhagem , Fenótipo , Receptores Citoplasmáticos e Nucleares/genéticaRESUMO
The major problem of many newly developed pharmaceutical drugs is their poor solubility in water and simultaneously in organic media. To solve these problems formulation as nanosuspensions is an attractive alternative. During the drug development process screening for an optimal formulation by homogenisation is essential. Time and cost effective production in an initial phase of R&D can be conducted on lab scale by using the Micron Lab 40 in its discontinuous version. In this report reproducibility of small scale production parameters (particle size, size distribution, content of microparticles) was exemplary studied for the drug RMKP22.
Assuntos
Preparações Farmacêuticas/química , Suspensões/química , Morfolinas/química , Tamanho da Partícula , Pteridinas/química , Reprodutibilidade dos Testes , Solubilidade , Espectrofotometria/métodosRESUMO
An unusual case of adenocarcinoma of the prostate metastatic to the mandibular condyle that presented clinically as a parotid tumor is reported. Standard radiologic studies may be misleading in such cases, and a high index of suspicion is required for atypical masses in the parotid region.
