ABSTRACT
Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.
Subject(s)
Pluripotent Stem Cells/metabolism , Animals , Cells, Cultured , Chromosomes, Mammalian/genetics , Karyotyping , Male , Pluripotent Stem Cells/cytology , Rats , Rats, Inbred WFABSTRACT
Albright hereditary osteodystrophy (AHO) is a condition with characteristic physical findings (short stature, obesity, round face, brachydactyly) but variable biochemical changes (pseudohypoparathyroidism, pseudopseudohypoparathyroidism). Most patients with AHO have decreased activity of the guanine nucleotide-binding protein (GS protein) that stimulates adenylyl cyclase. The gene encoding the alpha subunit of the GS protein (GNAS1) has been mapped to the long arm of chromosome 20. We describe 4 unrelated individuals with apparent AHO, associated with small terminal deletions of chromosome 2. All 4 patients had normal serum calcium levels consistent with pseudopseudohypoparathyroidism. Del(2) (q37) is the first consistent karyotypic abnormality that has been documented in AHO [Phelan et al., 1993: Am J Hum Genet 53:484]. The finding of the same small terminal deletion in 4 unrelated individuals with a similar phenotype suggests that a gene locus in the 2q37 region is important in the pathogenesis of Albright syndrome. The association of Albright syndrome and the GNAS1 locus on chromosome 20 is well documented. The observation of a second potential disease locus on chromosome 2 may help explain the heterogeneity observed in this disorder.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 2 , Fibrous Dysplasia, Polyostotic/genetics , Pseudopseudohypoparathyroidism/genetics , Adolescent , Calcium/blood , Child , Chromosome Mapping , Female , Fibrous Dysplasia, Polyostotic/diagnostic imaging , Humans , Male , RadiographyABSTRACT
Serum thyroxine values were determined prospectively over a 6-month interval in 97 newborn infants with birth weight < 2200 gm or gestational age < 37 weeks. There were 89 survivors and 8 deaths. Infants with thyroxine values of < 2.5 micrograms/dl (32.2 nmol/L) had a significantly higher mortality rate (p < 0.001) compared with infants with higher thyroxine levels. In neonates there may exist a critical thyroxine value below which there is an increased risk of mortality.
Subject(s)
Hypothyroidism/prevention & control , Infant Mortality , Neonatal Screening , Thyroxine/deficiency , Birth Weight , Female , Follow-Up Studies , Gestational Age , Humans , Infant , Infant, Newborn , Male , Predictive Value of Tests , Prospective Studies , Regression Analysis , Risk Factors , Thyroxine/blood , Time FactorsABSTRACT
A patient with partial duplication 2q and partial deficiency 11q is reported. The propositus was delivered at 30 weeks gestation, with a birth weight of 1,390 g. He had severe hyaline membrane disease, intraventricular hemorrhage, bronchopulmonary dysplasia, hypotonia, psychomotor retardation, hearing loss, and other anomalies including a short bitemporal diameter, prominent occiput, low-set ears, exophthalmos, short nose with depressed nasal root, downturned mouth corners, narrow high-arched palate, micrognathia, a deep longitudinal groove over the sacrococcygeal region, clinodactyly, and abnormal dermatoglyphics. Chromosome analysis showed the following karyotype: 46,XY,der11,t(2:11)(q32.2;q25)pat.
