Genetic and environmental influences on human birth weight

Path-analytic techniques were used to demonstrate a significant influence of both fetal genes and maternal environment on birth weight in a sample of infants born to primarily white, middle-class, nonsmoking mothers. If the mother smoked before conception, however, the expression of the fetal birth-weight genes in males was significantly reduced. Multiparity was associated with an increase in genetic variance. This is the first report that genetic influences on birth weight are dependent on the environmental conditions imposed on the fetus by the mother.     

Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE--To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN--Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING--Nottingham. SUBJECTS--147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES--Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS--Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS--These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.     

A comparison of mutation induction at the tk and hprt loci in human lymphoblastoid cells; quantitative differences are due to an additional class of mutations at the autosomal tk locus

X-Rays, ethyl methanesulfonate and ICR-191 induced 2 classes of trifluorothymidine-resistant mutants at the autosomal tk locus in human lymphoblastoid cells. These classes were differentiated by their growth rates; some mutants grew with a normal doubling time of 14-18 h (tk-NG), while others grew much more slowly, with doubling times of 21-44 h (tk-SG). Only mutants with normal growth rates were observed at the X-linked hprt locus; the frequencies of mutations induced at hprt were equal to those induced for tk-NG mutants. Thus, more mutations overall (by up to a factor of 6) were induced at tk than at hprt. These results are discussed in relation to recent studies in rodent cells, in which much greater mutation frequencies were observed at autosomal loci.     

Molecular characterization of thymidine kinase mutants of human cells induced by densely ionizing radiation

In order to characterize the nature of mutants induced by densely ionizing radiations at an autosomal locus, we have isolated a series of 99 thymidine kinase (tk) mutants of human TK6 lymphoblastoid cells irradiated with either fast neutrons or accelerated argon ions. Individual mutant clones were examined for alterations in their restriction fragment pattern after hybridization with a human cDNA probe for tk. A restriction fragment length polymorphism (RFLP) allowed identification of the active tk allele. Among the neutron-induced mutants, 34/52 exhibited loss of the previously active allele while 6/52 exhibited intragenic rearrangements. Among the argon-induced mutants 27/46 exhibited allele loss and 10/46 showed rearrangements within the tk locus. The remaining mutants had restriction patterns indistinguishable from the TK6 parent. Each of the mutant clones was further examined for structural alterations within the c-erbA1 locus which has been localized to chromosome 17q11-q22, at some unknown distance from the human tk locus at chromosome 17q21-q22. A substantial proportion (54%) of tk mutants induced by densely ionizing radiation showed loss of the c-erb locus on the homologous chromosome, suggesting that the mutations involve large-scale genetic changes.     

A spectrophotometric procedure for the determination of objective measurements of equine spermatozoan motility

A spectrophotometric procedure was developed and evaluated for the objective measurement of equine spermatozoan motility. A 100 mul sample of a sperm suspension, prepared by the removal of seminal plasma, was layered under a column of optically clear medium in a specially designed spectrophotometric cuvette maintained at 37 degrees C. Changes in light transmittance above the interface of the sperm suspension and medium were recorded on chart paper. As sperm cells swam into the medium, a decrease in light transmittance was recorded as a deflection on the chart paper. Chart recordings were analyzed for the height (cm) and time (min) to the peak deflection. To standardize the procedure, a fixed number of cells (1x10(9)) were used to prepare suspensions of 300x10(6) cells/ml. Coefficients of variation for mean values obtained under these conditions after the evaluation of five ejaculates from a given stallion were estimated at between 10 and 12%. Correlations between swim-up measurements and computer-assisted semen analysis demonstrated that the percentage of motile cells and mean velocity (mum/sec) of motile cells influenced swim-up measurements. Described here is a simple and inexpensive procedure to determine objective measurements of spermatozoan motility that may have application in semen evaluation and fertility testing in the stallion.     

The glue protein of ribbed mussels (Geukensia demissa): a natural adhesive with some features of collagen

Summary The Atlantic ribbed musselGeukensia (Modiolus)demissa attaches itself to the roots of cord grass and other hard objects in tidal salt marshes by spinning adhesive byssal threads. The precursor of a protein apparently present in the adhesive plaques of the threads was isolated in quantity from the foot of the mussel. The protein has an apparent molecular weight of 130000, a pI of 8.1, and contains a high proportion of Gly, Glu/Gln, Lys and 3,4-dihydroxyphenyl-l-alanine (DOPA). Sequence of tryptic peptides suggests a pattern of repeated motifs, such as: Gly-DOPA-Lys, and X-Gly-DOPA-Y-Z-Gly-DOPA/Tyr-Lys, where X is Thr or Ala in octapeptides and Gln-Thr in nonapeptides. Y is variable, but more often than not hydrophobic; and Z is frequently Pro or 4-trans-hydroxyproline (Hyp). The presence of Pro-Gly and Hyp-Gly sequences of -hydroxylysine in the protein is reminiscent of typical collagens; however, the protein is not labile to clostridial collagenase, nor does collagen cross-react with antibodies raised against the mussel protein. Unlike typical collagens, Gly probably occurs only at every 4th or 5th residue in this unusual mussel protein.Abbreviations Anti-Gdfp anti-G. demissa foot protein - Dopa 3,4-dihydroxyphenylalanine - CTAB cetyltrimethylammonium bromide - HPLC high performance liquid chromatography - PAGE polyacrylamide gel electrophoresis Supported by grants from the National Science Foundation (DMB 8500301) and the Office of Naval Research (N00014-86K-0717)     

Embryonic heart mesenchymal cell migration in laminin

Laminin, a large glycoprotein and major component of basement membranes, influences cell adhesion, migration, morphology, and differentiation. A peptide sequence, YIGSR, from the B1 chain of laminin has been found to correspond to an active site for cell adhesion. We report here that cardiac mesenchymal cells migrate vigorously within three-dimensional gels of laminin and that the YIGSR peptide will completely abolish this migratory activity. In contrast, migration of the mesenchymal cells into three-dimensional gels composed of collagen or collagen + laminin is not effected by YIGSR or other peptides (GRGDS, GRGDTP) reported to mediate cellular adhesion.     

HIV testing in patients with end stage renal disease.

One hundred and twenty eight British and Irish nephrologists were questioned about their policy for HIV testing of patients with end stage renal failure being considered for renal replacement therapy. A total of 101 (79%) replied. In the case of candidates for dialysis roughly one third of respondents tested only people they considered at risk of infection with HIV and nearly one fifth considered testing unnecessary. In the case of candidates for transplantation routine HIV testing was carried out by 68 of 100 nephrologists; 22 tested only patients "at risk" and 10 did not test. A positive HIV test result was considered by most but not all respondents (63/86) to exclude patients from transplantation. Twenty four of 88 nephrologists considered that HIV positivity should exclude patients from haemodialysis, but only seven of 87 would exclude such patients from peritoneal dialysis. Similar attitudes pertained for patients with end stage renal failure who refused HIV testing. Testing with the patient''s knowledge and consent was the policy of two thirds of nephrologists, but a patient''s signature was obtained by only 24 of 88. There should be a consensus on practice for HIV testing of patients with end stage renal failure.