Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Physical growth of primary school children of Lucknow

Conclusion From the above consideration we conclude that the stature of the boys and girls in all the age groups grew more rapidly than the other body segments under consideration. On the other hand, the arm girth grew very slowly. The mean values were progressively higher while the rate of growth and growth velocities were different in different age groups. The mean values of the lower extremity and biacromial indices were nearly constant in all the age groups which showed relatively equal growth of the stature in relation to lower extremity and shoulder breadth. From the Department of Anthropology, Lucknow University, Lucknow-226001.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Laparoscopic and ultrasound-guided transcervical evacuation of cornual ectopic pregnancy: an alternative approach.

Conventional treatment of cornual ectopic pregnancy carries significant morbidity and may compromise future fertility. We present a minimal access technique for the treatment of cornual ectopic pregnancies which we believe carries a reduced morbidity and may be less likely to compromise future reproductive function.     

Approaches to Preceramic Polymer Fiber Fabrication and On-Demand Applications

The demand for lightweight, high-modulus, and temperature-resistant materials for aerospace and other high-temperature applications has contributed to the development of ceramic fibers that exhibit most of the favorable properties of monolithic ceramics. This review demonstrates preceramic-based polymer fiber spinning and fiber classifications. We discuss different types of fiber spinning and the advantages of each. Tuning the preceramic polymer chemical properties, molar mass, functional chemistry influences, and incorporation with fillers are thoroughly investigated. Further, we present the applications of preceramic-based polymer fibers in different fields including aerospace, biomedical, and sensor applications. This concise review summarizes recent developments in preceramic fiber chemistry and essential applications.     

A Study of Erosion–Corrosion Behaviour of Friction Stir-Processed Chromium-Reinforced NiAl Bronze Composite

Corrosion is frequently viewed as a catastrophic and unavoidable disaster in marine applications. Every year, a huge cost is incurred on the maintenance and repair of corrosion-affected equipment and machinery. In the marine environment, as-cast nickel–aluminium bronze (NAB) is susceptible to selective phase corrosion. To solve this problem, chromium-reinforced nickel–aluminium bronze was fabricated using the friction stir process (FSP) with improved microstructures and surface properties. A slurry erosion–corrosion test on as-cast and FSPed composites demonstrated that the developed surfaced composite has lower erosion and corrosion rates than the as-cast NAB alloy. The erosion–corrosion rate increased with a decrease in the impact angle from 90° to 30° for both as-cast NAB and prepared composites, exhibiting a shear mode of erosion. The specimens at impact angle 30° experienced more pitting action and higher mass loss compared with those at impact angle 90°. Due to increases in the mechanical properties, the FS-processed composite showed higher erosion resistance than the as-cast NAB alloy. Furthermore, corrosion behaviour was also studied via the static immersion corrosion test and electrochemical measurements under 3.5 wt.% NaCl solution. In a static immersion corrosion test, the FSPed composite outperformed the as-cast NAB composite by a wide margin. The FSPed composite also demonstrated a reduced electrochemical corrosion rate, as revealed by the polarization curve and electrochemical impedance spectroscopic (EIS) data. This reduced rate is attributed to the formation of a Cr oxide film over its surface in the corrosive environment.