Further studies on the effect of nucleotides upon expression of the folate sensitive fragile sites have confirmed that high concentrations of thymidine (300 mg/l) but not BrdU (600 mg/l) induce these fragile sites. Induction by thymidine can be suppressed by addition of cytidine in a dose response manner. Studies on other nucleotides suggest that guanosine, but not adenosine or cytidine, can induce the fragile sites. The previously hypothesised model for the DNA at a fragile site as a naturally occurring polypurine/polypyrimidine sequence which becomes amplified is further developed.

Adenosine↗

PubMedDate not supplied

Prenatal diagnosis of the fragile X--the Australasian experience.

Identification of increasing numbers of females heterozygous for fragile X linked mental retardation together with improved genetic counselling is creating a growing demand for prenatal diagnosis of fra(X). However, present cytogenetic techniques are somewhat unreliable and our collaborative approach has endeavoured to improve quality of cell culture systems and the sensitivity of fra(X) detection. Since 1985 we have exchanged cell cultures between our laboratories for verification of diagnostic results and comparison of induction techniques and have benefitted from larger numbers of cells scored for fra(X). Our 50 cases represent almost all of such studies undertaken in Australasia (Australia and New Zealand). Ten cases were unequivocally fra(X) positive; there was discrepancy between laboratories in 4 cases and one false-negative case. We propose a protocol to enhance fra(X) detection and conclude that, provided care is exercised, couples at risk of a fra(X) pregnancy can benefit from prenatal cytogenetic diagnosis.

Amniocentesis↗

PubMedDate not supplied

The mechanisms of iron uptake by fetal rat hepatocytes in culture.

The mechanisms of iron accumulation by cultured hepatocytes isolated from fetal rat liver (19 days gestation) were investigated using rat transferrin labeled with 125I and 59Fe. The rates of iron and transferrin internalization by the cells were measured by incubating the hepatocytes with the labeled transferrin at 37 degrees C followed by treatment with pronase at 4 degrees C to remove surface-bound transferrin and iron. Iron internalization increased linearly with time. Approximately 65% of the internalized iron was incorporated into ferritin. In contrast to iron, the rate of transferrin internalization was biphasic, with a rapid phase during the first 10 to 15 min and a second slower phase which becomes more apparent after that time. Iron and transferrin internalization were temperature-dependent. Chase experiments showed that the internalized transferrin donated all of its iron to the cell and was then released in a biphasic manner which was dependent on the time of preincubation with radiolabeled transferrin. These experiments showed that iron uptake occurs by at least three processes. The first mechanism involves the specific receptor-mediated endocytosis of transferrin. Each cell has an average of 7.8 +/- 1.0 X 10(5) (mean +/- SE, n = 5) transferrin binding sites with an apparent association constant of 2.0 +/- 0.4 X 10(6) M-1. The second process is nonsaturable up to a transferrin concentration of at least 6 microM but like the specific process, also leads to accumulation of iron in excess of transferrin. It involves the endocytosis of transferrin mediated by 4.2 X 2.6 X 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Impact of transjugular intrahepatic portosystemic shunt on orthotopic liver transplantation.

Transjugular intrahepatic portosystemic shunt (TIPS) is being increasingly utilized prior to liver transplantation for portal hypertensive bleeding refractory to sclerotherapy or as initial management of variceal bleeding. The impact of TIPS on subsequent orthotopic liver transplantation (OLT) is uncertain. The purpose of this study was to analyze the effect of TIPS on OLT in terms of operative transfusion requirements, operative time, length of hospital stay, and graft and patient survival. The results in 17 patients undergoing TIPS for control of initial or recurrent variceal bleeding prior to OLT between June 1991 and December 1992 were compared to two other groups undergoing transplantation: 32 control patients with a history of variceal bleeding not treated by TIPS and 11 patients with a previous surgical portosystemic shunt. Compared with control and surgical shunt patients, patients who underwent TIPS had less transfusion requirement for packed red blood cells and fresh frozen plasma during OLT. The operative time and hospital stay of the TIPS patients were slightly, but not significantly, less. In contrast to patients having TIPS, the patients with a history of a previous surgical shunt had an increased requirement for packed red blood cells, longer operative time, and longer stay in the intensive care unit and hospital. Two patients had recurrent variceal bleeding after TIPS; one patient was found to have an occluded stent, and the other patient (with a patent stent) responded to sclerotherapy. Of the 14 patients with ascites, 8 patients improved and 6 patients had complete resolution after TIPS. There were no major complications related to TIPS, although 3 patients had new or recurrent hepatic encephalopathy that was easily manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

SCE, X-radiation sensitivity and mutation rate in multiple sclerosis.

In order to detect any underlying DNA abnormality that may be present in multiple sclerosis (MS), the incidence of SCE, X-radiation sensitivity and the frequency of 6-thioguanine-resistant cells were determined in the lymphocytes of 34 MS patients. As a group, MS patients showed an increase in the SCE rate compared to control. However, there was no increase in X-radiation sensitivity. The frequency of 6-thioguanine-resistant mutant cells was also normal.

Crossing Over, Genetic↗

PubMedDate not supplied

Factors promoting cigarette smoking among black youth: a causal modeling approach.

A longitudinal model of Black adolescent smoking was tested using 223 seventh-grade students attending public schools in northern New Jersey. Interpersonal and intrapersonal factors were hypothesized to have an impact on Black seventh graders' decision to smoke. After conducting an exploratory Principal Factor Analysis (PFA) using a varimax rotation with the Time 1 data, a structural equation model was developed and refined through successive iterations. The final model revealed friends' smoking to be the most significant predictor of Black adolescent smoking at Time 1, but perceived smoking norms and intrapersonal factors such as decision making, self-efficacy, and self-esteem at home and at school exerted an important influence on smoking at Time 2. These results suggest that social influence factors may be important early in the smoking initiation process, but factors such as perceived smoking norms and intrapersonal factors may play an important role in maintaining the smoking habit in Black adolescents.

Adolescent↗

PubMedDate not supplied

Food allergy.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

The desferrithiocin (DFT) class of iron chelators: potential as antineoplastic agents.

Iron (Fe) is essential for the proliferation of cancer cells. A subgroup of the orthosubstituted phenolate class of Fe chelators, desferrithiocin [2-(3'-hydroxypyrid-2'-yl)4-methyl-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its analogues, have potential application in short-term chemotherapy for cancer by Fe deprivation. Their effects on cell proliferation, cell cycle progression, Fe uptake and toxicity were therefore examined in adult and fetal rat and human hepatocellular carcinoma (HCC) cell lines, as well as in normal cells. DFT was more active than desferrioxamine, in clinical trials as an antineoplastic agent, consistently inhibiting cell proliferation in all cell lines (IC50 = 40 microM). 2-(2'-hydroxyphenyl-2'-yl)-delta2-thiazoline-4(S)-carboxylic acid was the most active analogue (IC50 = 55-90 microM). Inhibition was affected by chelator concentration and ability to prevent Fe uptake. The fetal-cell-derived HCC was more susceptible than adult HCC. Structure-activity studies revealed that thiazol methyl deletion greatly diminished antiproliferative activity of the chelators but stereochemical orientation of COOH around C4 had no effect. Removal of the N from the pyridine ring restored antiproliferative activity. Chelators inhibited DNA synthesis in the S phase. The chelators at their IC50 concentration had little or no effect on Fe uptake in normal cells. This apparent selectivity of these chelators for cancer cells, coupled with their high activity, suggests that further investigation is warranted.

Animals↗

PubMedDate not supplied

Organization and chromosomal localization of the human interleukin 5 receptor alpha-chain gene.

The gene for the hIL-5R alpha subunit, which is present in a single copy in the human genome, has been analysed in detail. It is located on chromosome 3 in the region 3p26. The gene organization reflects its relationship to the cytokine/haematopoietin receptor superfamily. Three introns are located in the 5' untranslated region. The subsequent exons determine the functional domains of the hIL-5R alpha protein: the signal peptide, three fibronectin type III-like (FN-like) modules, each built up by two exons, the membrane anchor and two exons forming the cytoplasmic tail, the first of which contains the proline cluster region. In addition, a specific exon generating a soluble isoform is located before the membrane anchor exon. This specific exon contains an in frame TAA stop codon, followed by a polyadenylation signal. Hence, a normal splicing event leads to a soluble IL-5R alpha variant, whereas alternative splicing is required for cell membrane anchoring. A second area of alternative splicing is found in the 5' leader sequence, and possibly relates to the presence of short open reading frames preceding the main ATG. All intron-exon junctions meet the GT-AG rule. The gene structures of all cytokine/haematopoietin receptors documented so far have also been compared with respect to intron phasing. This shows that all introns between the FN-III-like modules are of the +1 type, but in addition, splice sites within the Cys-module and WS-WS-module are invariably of the +2 and 0 type, respectively.

Amino Acid Sequence↗

PubMedDate not supplied

A psychosocial approach to smoking prevention for urban black youth.

Despite the high rates of smoking-related cancers among black Americans, little is known about the type of smoking prevention program that might be effective with black youth. The current study pilot-tested a promising smoking prevention approach to determine its feasibility, acceptability, and effectiveness. A total of 608 students in nine predominantly black urban junior high schools were stratified by community and randomly assigned to treatment and control conditions. Students in the treatment condition participated in a 12-session smoking prevention program which taught resistance skills and general life skills. Process data indicated that this prevention approach was feasible and acceptable to students, teachers, and administrators. Outcome data indicated that this program reduced the proportion of children who smoked in the past month by 56 percent, and it increased knowledge of the adverse consequences of smoking and normative expectations concerning adult and peer smoking. These results are discussed in terms of their implications for prevention and modifications which might further strengthen the efficacy of this approach for urban black adolescents.

Adaptation, Psychological↗