Prenatal diagnosis of fragile X syndrome by direct detection of the unstable DNA sequence.
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Base Sequence↗
Biomedical subjects
S Yu
Publications and source records attributed to S Yu.
Hereditary unstable DNA: a new explanation for some old genetic questions?
Fragile X syndrome, associated with the fragile X chromosome, is the most common cause of familial mental retardation. The condition is characterised by a heritable DNA sequence that consists of an abnormal number of CCG repeats, and which is unstable in both mitosis and meiosis. We suggest that such heritable unstable DNA sequences could be present in other parts of the genome and that these might explain a number of genetic events that are not well understood in terms of classic genetic mechanisms. Such poorly explained observations include anticipation, incomplete penetrance, variable expression, and possibly imprinting, variegation, and multifactorial inheritance.
Chromosome Fragility↗
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n.
The sequence of a Pst I restriction fragment was determined that demonstrate instability in fragile X syndrome pedigrees. The region of instability was localized to a trinucleotide repeat p(CCG)n. The sequence flanking this repeat were identical in normal and affected individuals. The breakpoints in two somatic cell hybrids constructed to break at the fragile site also mapped to this repeat sequence. The repeat exhibits instability both when cloned in a nonhomologous host and after amplification by the polymerase chain reaction. These results suggest variation in the trinucleotide repeat copy number as the molecular basis for the instability and possibly the fragile site. This would account for the observed properties of this region in vivo and in vitro.
Base Sequence↗
Fragile X genotype characterized by an unstable region of DNA.
DNA sequences have been located at the fragile X site by in situ hybridization and by the mapping of breakpoints in two somatic cell hybrids that were constructed to break at the fragile site. These hybrids were found to have breakpoints in a common 5-kilobase Eco RI restriction fragment. When this fragment was used as a probe on the chromosomal DNA of normal and fragile X genotype individuals, alterations in the mobility of the sequences detected by the probe were found only in fragile X genotype DNA. These sequences were of an increased size in all fragile X individuals and varied within families, indicating that the region was unstable. This probe provides a means with which to analyze fragile X pedigrees and is a diagnostic reagent for the fragile X genotype.
Chromosome Mapping↗
Restoration of lymphocyte proliferation and CTL generation by murine rIL-2 after treatment of allogeneic stimulator cells by ultraviolet B irradiation, heat, or paraformaldehyde.
Following a 5-day mixed lymphocyte culture (MLC), C3H/HeJ (H-2k) splenocytes stimulated with DBA/2 (H-2d) gamma-irradiated splenocytes (2000 rads) are specifically cytotoxic in a 4-hr 51Cr-release assay to P815 (H-2d) target cells (62 +/- 2% cytolysis) but not to third-party EL4 (H-2b). However, when the DBA/2 stimulator cells were treated with heat inactivation (45 degrees C for 1 hr), fixed with 1% paraformaldehyde (15 min), or irradiated with ultraviolet-B light (10(4) J/M2), no cell proliferation or cytolytic activity developed in the MLCs. The levels of IL-1, IL-2, and IL-6 from the supernatants of MLC using stimulators undergoing either of the three treatments were markedly decreased compared with that from gamma-irradiated stimulators. Both cell proliferation and specific cytolysis were restored in a dose-dependent fashion by the addition of murine rIL-2 to the MLCs. If the stimulator cells were first activated with 5 micrograms/ml pokeweed mitogen or lipopolysaccharide for 2 days, the subsequent treatment with heat, paraformaldehyde, or UV-B did not significantly affect the development of cytolysis (54-70% cytolysis). Suppressor cells were not detected when cells from the nonresponsive MLCs (2.5 x 10(6) cells) were added to an MLC freshly prepared with gamma-irradiated stimulator cells, or were injected intraperitoneally (50 x 10(6) cells) into naive mice 2 days before recovery and in vitro sensitization of splenocytes. Therefore, modification of the stimulating alloantigen can prevent the release of cytokines that function as an essential second signal in the development of the proliferative response and subsequent cytolysis. The cytokine found to be essential for restoration of this response is IL-2.
Animals↗
Fragile X syndrome: genetic localisation by linkage mapping of two microsatellite repeats FRAXAC1 and FRAXAC2 which immediately flank the fragile site.
We report the genetic localisation of the fragile site at Xq27.3 associated with fragile X syndrome. The position of the fragile site within the multipoint linkage map was determined using two polymorphic microsatellite AC repeat markers FRAXAC1 and FRAXAC2. These markers were physically located within 10 kilobases and on either side of the p(CCG)n repeat responsible for the fragile site. FRAXAC1 has five alleles with heterozygosity of 44% and is in strong linkage disequilibrium with FRAXAC2 which has eight alleles and a heterozygosity of 71%. No recombination was observed either between these markers in 40 normal CEPH pedigrees or with the fragile X in affected pedigrees. These markers provide the means for accurate diagnosis of the fragile X genotype in families by rapid polymerase chain reaction analysis and were used to position the fragile X within the multipoint map of the X chromosome to a position 3.7 cM distal to DXS297 and 1.2 cM proximal to DXS296.
Base Sequence↗
Effects of barbiturates on GABA system: comparison to alcohol and benzodiazepines.
Central nervous system depressants, e.g. barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This proceeding briefly summarizes the evidence presented in our previous review (Yu S and Ho Ik: Alcohol 7: 261, 1990) as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also discussed. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.
Animals↗
[Photosensitizing effects of tetracycline, chlorophyll and hematoporaphyrin derivatives on laser ablation of atherosclerotic plaques].
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Animals↗
The therapeutic and biological effects of total lymph node irradiation and autologous bone marrow infusion on malignant lymphoma patients.
Forty patients with malignant lymphoma were treated by 60Co total lymphoid irradiation (TLI): 21 cases received 6 Gy and 19 received 8 Gy. Ten also received autologous bone marrow infusion (ABMI). Acute radiation damage with digestive tract reaction and hemopoietic and immunological depression was observed. Bone marrow was depressed. WBC and platelets decreased rapidly. Lymphocytes showed quantitative and qualitative changes even at the early stage. All these symptoms subsided within 40 days. TLI accompanied by irradiation of the tumor site could result in effective control. The 1-, 3-, and 5-year survival rates of malignant lymphoma patients were 30/40 (75%), 14/24 (58%) and 4/12 (33%), respectively, while in those with Hodgkin's disease alone, the 1- and 3-year survival rates were 10/13 (76%) and 5/7 (71.4%), respectively. ABMI hastened hemopoietic reconstitution, which recovered relatively quickly after TLI.
Adolescent↗
[Field survey of sarcocystis infection in the Tibet autonomous region].
Fecal specimens of 926 persons from Duilongdeqing, Milin and Linzhi counties of Tibet were examined by the zinc sulfate flotation method. The prevalences of Sarcocystis hominis in the three counties were 20.5%, 22.5% and 22.9% respectively (P greater than 0.05), with an average of 21.8%, and those of Sarcocystis suihominis were 0, 0.6% and 7.0% respectively (P less than 0.01). No significant difference in infection rate was found between different age or sex groups. Sarcocystis was detected in 42.9% of beef specimens from the market. Obviously, sarcocystis infection in Tibetans is usually caused by eating raw or undercooked beef or pork. The infected cases were generally asymptomatic, 9/10 and 5/5 of cases showed negative stool examination one month after being treated by sulfadiazine or finidazole respectively.
Animals↗
[Miliary tuberculosis. Report of 4 cases proved by autopsy].
Four cases of acute miliary tuberculosis, including one case of nonreactive tuberculosis, are reported in this article. Final diagnoses were proved by autopsy. Literature review shows that symptoms of the disease vary greatly in different cases, but fever with unknown causes and overwhelming infection is the constant features. Nonreactive tuberculosis is common in the patients with low immunity and correct diagnosis depends on autopsy in most cases. Anti-tuberculosis drugs for nonreactive tuberculosis is not very effective and the prognosis is unfavourable. This article provides for the doctors with the experience of mis-diagnosis of acute miliary tuberculosis, especially nonreactive tuberculosis.
Aged↗
Isolation of a human DNA sequence which spans the fragile X.
To identify the sequences involved in the expression of the fragile X and to characterize the molecular basis of the genetic lesion, we have constructed yeast artificial chromosomes (YACs) containing human DNA and have screened them with cloned DNA probes which map close to the fragile site at Xq27.3. We have isolated and partly characterized a YAC containing approximately 270 kb of human DNA from an X chromosome which expresses the fragile X. This sequence in a yeast artificial ring chromosome, XTY26, hybridizes to the two closest DNA markers, VK16 and Do33, which flank the fragile site. The human DNA sequence in XTY26 also spans the fragile site on chromosome in situ hybridization. When a restriction map of XTY26, derived by using infrequently cutting restriction enzymes, is compared with similar YAC maps derived from non-fragile-X patients, no large-scale differences are observed. This YAC, XTY26, may enable (a) the fragile site to be fully characterized at the molecular level and (b) the pathogenetic basis of the fragile-X syndrome to be determined.
Chromosome Mapping↗
[Research on the processing of Angelica based on the analysis of water soluble constituents].
In this paper, a comparative study on the contents of water-soluble and alcohol-soluble tannin and ferulic acid in Angelica and its processed products is reported. The result shows that different processing methods have significant effects on the above constituents, thus administering to the interpretation of the theory of Angelica processing.
Coumaric Acids↗
Magnetic resonance imaging and anatomy of the spine.
This article deals with the detailed anatomy of the spine most pertinent to magnetic resonance (MR) imaging. The cervical and lumbar regions, the pediatric spine, and the intervertebral discs are emphasized. High resolution MR images of cadaver spines obtained from a 1.5 tesla imager were compared with cryomicrotome sections. This correlative study provided meaningful anatomic information for accurately interpreting and better understanding MR images of living patients.
Cervical Vertebrae↗
A BclI RFLP for DXS296 (VK21) near the fragile X.
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Deoxyribonucleases, Type II Site-Specific↗
Effects of GABA antagonists, SR 95531 and bicuculline, on GABAA receptor-regulated chloride flux in rat cortical synaptoneurosomes.
Synaptoneurosomes isolated from cerebral cortices of male Sprague-Dawley rats were used for studying GABAA receptor-regulated chloride influx. The in vitro effects of GABA antagonists, SR 95531 (a pyridazinyl GABA derivative) and bicuculline, on pentobarbital-stimulated, muscimol-stimulated or flunitrazepam-enhanced, muscimol-stimulated chloride uptake were studied. The chloride uptake was determined at 30 degrees C, for 5 sec. Pentobarbital and muscimol produced a maximal stimulation of chloride uptake in cortical synaptoneurosomes at 500 microM and 50 microMs, respectively. SR 95531 as well as bicuculline had no effect on the basal uptake of chloride. Whereas, SR 95531 (0.3 - 30 microM) and bicuculline (0.1 - 100 microM), when added 5 min before muscimol (50 microM), produced a significant concentration-dependent inhibition of muscimol (50 microM)-stimulated chloride uptake (IC50S of 0.89 +/- 0.11 microM and 13.45 +/- 2.10 microM, respectively). In studies of the inhibitory effects of SR 95531 and bicuculline on pentobarbital (500 microM)-stimulated chloride uptake, the IC50S were 0.81 +/- 0.12 microM and 3.86 +/- 1.14 microM, respectively. SR 95531 exhibited a more potent inhibitory effect than bicuculline on flunitrazepam-enhanced, muscimol-stimulated chloride uptake. The results revealed that SR 95531 has a more potent antagonistic effect than bicuculline on GABAA-regulated chloride flux.
Animals↗
Augmentation of cell-mediated cytotoxicity following 50% partial hepatectomy.
The cytolytic responses of C3H/HeJ mice after 50% hepatectomy (PH) were assessed in a 4-hr 51Cr-release assay. Spleen cells (SC) (50 x 10(6] from normal or PH C3H/HeJ (H-2k) mice were sensitized with equal numbers of irradiated allogeneic DBA/2 (H-2d) spleen cells in a five-day mixed lymphocyte culture. Generated cytolytic activity was measured against 51Cr-labeled P815 mastocytoma (H-2d) and EL4 lymphoma (H-2b) target cells. The wet weight and cell numbers per spleen following 50% partial hepatectomy were 70% and 75% higher than the control values for the first 20 days, and then returned to normal levels by 21 days. The cytolysis by spleen cells from 2-, 14-, and 31-day PH mice were 89.3 +/- 0.7, 86.9 +/- 5.3, and 90.1 +/- 1.3%, respectively, compared with control (sham-operated) values of 56.0 +/- 1.0, 57.0 +/- 2.0, and 49.9 +/- 7.0% (P less than 0.03 at E/T 100:1). This enhanced cytolysis by PH spleen cells remained high for at least 118 days after the liver resection before returning to control levels by 268 days. Cytolytic effector cells in PH SC were generated at least 24 hr earlier than in control SC. When normal and PH cytolysis were compared following primary and secondary in vitro sensitization, the cytolytic levels of primarily-sensitized PH spleen cells were comparable to secondarily sensitized normal spleen cells. Furthermore, the primarily sensitized normal spleen cells did not show crossreactive cytolysis with EL4 target cells (H-2b), while both the primarily sensitized PH spleen cells and the secondarily sensitized normal spleen cells were significantly cross-reactive against the third party EL4 target cells. Adherent PH spleen cells appear to be responsible for this augmented cytolytic capacity since their coculture with normal nonadherent responder spleen cells increased control cytolysis by approximately 30%. These studied demonstrate that, following 50% partial hepatectomy, there is an immediate and sustained increase in the allospecific cytolytic response.
Animals↗
Effect of axial loading on neural foramina and nerve roots in the lumbar spine.
The hypothesis that the neural foramina in some patients are critically narrowed by axial compression of the spine has not been studied with direct imaging techniques. Frozen cadaveric motion segments of the lumbar spine (intervertebral disk and contiguous vertebrae) were imaged with computed tomography (CT). The segments were thawed and compressed in a hydrostatic press to simulate axial loading, and then the segments were frozen and imaged again. The motion segments were subsequently sectioned with a cryomicrotome, and the chronic degenerative changes present in the disks were classified. Pre- and post-compression CT images were compared, and anatomic relationships were studied. In 41 randomly selected segments (some with preexisting radial, transverse, and concentric annular tears), compression diminished the diameters and cross-sectional areas of the spinal canal and neural foramina. In no cases were nerve roots displaced, distorted, or compressed by axial loading. This study suggests that axial loading, such as that produced by ordinary weight bearing, does not critically compromise the neural foramina even in the presence of chronic degenerative disk changes.
Adult↗