A molecular genetic approach to the identification of isochromosomes of chromosome 21

Summary The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are isochromosomes derived from a single parental chromosome 21.     

Chromosome distribution of intracisternal A-particle sequences in the Syrian hamster and mouse

Metaphase chromosomes of Syrian hamster and BALB/c mice were hybridized in situ with radiolabeled probes derived from cloned intracisternal A-particle (IAP) genes of the corresponding species. The DNAs of these species are known to contain about 900 and 1,000 copies, respectively, of the retrovirus-like IAP sequence elements per haploid genome. Multiple IAP sequences were found on all chromosomes of both hamster and mouse. In the hamster, more than half of the IAP sequences were located in regions of non-centromeric constitutive heterochromatin, at an average concentration per unit chromosome length 5 times greater than in the euchromatic regions. The other dispersed sequences showed marked local variations in concentration along the chromosome lengths; both discrete foci and large grain clusters were observed as well as regions apparently lacking IAP sequences. Within the resolution of the techniques, IAP sequences appeared to be more evenly distributed over the mouse chromosomes; however, some prominent variations in concentration were seen. The number of potentially active IAP genes in the Syrian hamster, and by extension in the mouse, may be restricted by the preferential location of IAP sequences in genetically inert regions of the genome.     

Leukotriene C4 Transport and Metabolism in the Central Nervous System

The transport and metabolism of radiolabeled leukotriene (LT) C4 in the CNS were investigated after intraventricular injection. Under thiopental (Pentothal) anesthesia, New Zealand white rabbits were injected intracerebroventricularly with 0.2 ml of artificial CSF containing 2.5 microCi of [3H]LTC4 (36 Ci/mmol), 0.3 microCi of [14C]mannitol, and, in some cases, 0.9 mg of probenecid, 1.8 mg of cysteine, 1.4 micrograms of unlabeled LTC4, or 2 mg of tolazoline HCl. After 2 h, the conscious rabbits were killed, and the quantity and nature of the 3H and 14C were determined in CSF, choroid plexus, and brain. The [3H]LTC4 recovered in CSF and brain was not extensively metabolized, as greater than 70% of the 3H remained [3H]LTC4, although some spontaneous conversion to 11-trans-[3H]LTC4 occurred. Oxidized forms of [3H]LTC4, [3H]LTD4, and [3H]LTE4 did not exceed 18% in CSF and brain. After intraventricular injection of [3H]LTC4, 3H was transferred from the CSF to blood by a probenecid-sensitive, but tolazoline-insensitive, transport system in the CNS much more rapidly than mannitol. Cysteine decreased the retention of [3H]LTC4 in brain. These results are consistent with previous in vitro observations that [3H]LTC4 is transferred from CSF into blood by an efficient transport system for LTC4 in choroid plexus.     

Behavioral treatment of irritable bowel syndrome: A 1-year follow-up study

Sixteen clients afflicted with irritable bowel syndrome (IBS) were reassessed 1 year following completion of a multicomponent treatment package incorporating progressive muscle relaxation, thermal biofeedback, cognitive therapy, and IBS education. For the 14 patients who kept a 2-week symptom diary, significant reductions in ratings of abdominal pain and tenderness, diarrhea, and flatulence were obtained comparing pretreatment and follow-up symptom-diary ratings. Eleven of 14 clients were improved over pretreatment levels, 57% met the criteria for clinical improvement of at least a 50% reduction in major symptom scores, and all but 1 of 16 rated themselves as subjectively improved.     

Computer-Assisted Image Analysis of Plant Growth, Thigmomorphogenesis, and Gravitropism

A nonintrusive auxonometric system, based on the DARWIN image processor (Telewski et al. 1983 Plant Physiol 72: 177-181), is described and demonstrated in the analysis of gravitropism and thigmomorphogenesis in corn seedlings (Zea mays). Using this system, growth and bending of regularly shaped plants or organs can be quickly and accurately measured without, in any way, interfering with the plant. Furthermore, the growth and bending curves are automatically plotted. Thigmomorphogenesis in the aerial part of corn seedlings involves growth promotion at a low force load and growth retardation at higher force loads. The time courses of the two kinds of response are somewhat different, with retardation occurring immeditely after mechanical perturbation and growth promotion taking somewhat longer to begin. Gravitropic experiments show that when dark-grown corn seedlings are placed on their side in the light, the resulting curvature is due to two consecutive morphological mechanisms. In the first instance, lasting for about 15 minutes, the elongation of the bottom edge of the plant accelerates, while the elongation of the top edge remains constant. After that, for the next 1.75 hours, the elongation of the top edge decelerates and stops while that of the bottom edge remains constant at the increased rate for most of the period. The measurements taken from both experiments at relatively high resolution (0.08-0.1 millimeter) show that the growth curves are not smooth but show many small irregularities which may or may not involve micronutations.     

Chlorophyll differences in Mono Lake (California) observable on Landsat imagery

In Mono Lake (California), a large saline lake, chlorophyll concentrations in the euphotic zone increased from 4 to 45 µg l^–1 between July and October 1979. These seasonal changes in chlorophyll are detectable on imagery obtained with the multispectral scanner on Landsat. Computer-compatible tapes of Landsat images were normalized for solar zenith and corrected for atmospheric scatter and absorption to obtain Landsat band 4 emittances (W m^–2 str^–1) of 13.4 ± 0.5 when chlorophyll was 4 µg l^–1 and 4.6 ± 0.3 when chlorophyll was 45 µg l^–1. Lake wide, spatial heterogeneity of chlorophyll of 2 µg l^–1 in July and 8 µg l^–1 in October was not detectable on the Landsat imagery.     

Reduction in headache patients' medical expenses associated with biofeedback and relaxation treatments

Comparisons are made of self-reported medical costs from a sample of headache patients who underwent various combinations of relaxation training and biofeedback training. The average costs for the 2 years prior to self-regulatory treatment were $955±480 (3 SEM) for 45 patients; for the 2 years after completing treatment the average costs were $52±28 (3 SEM) for patients. Within the limitations of the study, medical costs do seem to have been markedly reduced.This research was supported by a grant from NINCDS, NS-15235.