Synthesis of a trans-syn thymine dimer building block. Solid phase synthesis of CGTAT[t,s]TATGC.

The synthesis of a building block for the sequence specific introduction of the trans-syn thymine dimer into oligonucleotides via solid phase DNA synthesis technology is described. CGTAT[t,s]TATGC was synthesized in 48% overall yield by a partially automated procedure. The stepwise coupling yield for addition of the trans-syn thymine dimer building block was 58%. The dimer containing oligonucleotide was characterized by 500 MHz 1H COSY and NOESY spectroscopy and 202.5 MHz 31P NMR. The 1H chemical shifts for the trans-syn thymine dimer unit of the decamer were found to be quite similar to those found for the trans-syn thymine dimer of TpT. Upon photolysis at 254 nm, CGTAT[t,s]TATGC was converted to a major product which coeluted with authentic CGTATTATGC and a minor product which coeluted with authentic CGTAT[c,s]TATGC, further supporting the presence of an intact trans-syn thymine dimer unit.     

Breakage of the T cell receptor α chain locus in non malignant clones from patients with ataxia telangiectasia

Summary Patients with ataxia telangiectasia (A-T) develop specific chromosome translocations, which may confer a proliferative advantage, resulting in the appearance of large clones in the peripheral blood lymphocytes. These lymphocytes are not malignant. Using in situ hybridisation techniques we have investigated a consistent 14q11 translocation break-point observed in a t(X;14)(q28;q11) translocation clone from each of two different patients and a t(14;14)(q11;q32) clone from a third patient. In all cases the chromosome translocation involved breakage within the chain locus of the T cell receptor (TCR), between the variable and constant regions, at 14q11. Chromosome rearrangement involving breakage within TCR can therefore precede the development of malignancy. Further chromosomal rearrangement may be required in these patients, for progression to the leukaemic state.     

Synthesis and biological evaluation of pNPY fragments

Peptide fragments of pNPY corresponding to the C-terminal segments (13-36) and (25-36), the N-terminal segments (1-12) and (1-24), the segments (6-14) and (7-20), which contain a putative beta-turn, and the internal segments (13-24) and (20-30) were synthesized using solid phase methodology. These fragments were assayed for NPY receptor binding activity in the rat hypothalamus membrane preparation, enhancement of food intake in the rat following ivt administration and inhibition of electrically stimulated muscle contraction in the rat vas deferens. Only the C-terminal fragment (13-36) retained some of the activities of pNPY, appearing to act as a weak agonist, having an additive effect with pNPY on the inhibition of muscle contraction and prolonging the duration of action of pNPY in the feeding assay. It also had considerable alpha-helical character, as did pNPY. None of the other peptide fragments had any agonist or antagonist activity. These results suggest that the expression of full biological NPY activity requires both the C- and the N-terminal segments as well as a putative amphiphilic alpha-helical segment (14-31).     

Guidelines for the Control of Human Immunodeficiency Virus Infection in Adolescents

Although adolescents account for only 0.4% of reported cases of the acquired immunodeficiency syndrome (AIDS) in the United States, they are sexually active and, therefore, at risk of acquiring human immunodeficiency virus (HIV) infection. To address issues of HIV control in adolescents, we developed guidelines that emphasize education and medical care and deemphasize antibody testing. For adolescents known to be infected with HIV, we recommend no restrictions on access to educational or treatment programs except when their health providers recommend such restrictions to protect them from exposure to opportunistic infections. For adolescents of unknown antibody status with a possible previous exposure to HIV, we recommend that as long as the incidence of HIV infection and clinical AIDS remains low, there should be no restrictions on residential placements and no routine antibody testing.     

Fine structure,mechanism of heart function and haemodynamics in the prosobranch gastropod molluscLittorina littorea (L.)

Summary The heart, main blood vessels, and associated structures ofLittorina littorea were examined by scanning and transmission electron microscopy. The auricle is subdivided into two compartments, one receiving blood from the gill and opening to the nephridial gland vein, the other connecting with the latter anteriorly and the ventricle posteriorly.Video recordings were made of the beating heart in vivo and revealed that the auricle expelled blood not only to the ventricle, but also the nephridial gland vein at systole and provided further evidence of tidal flow of blood in the vein. There is clear indication that the constant volume mechanism of auricular re-filling is not strictly true inLittorina.Blood pressure in the heart and major vessels was measured using a servo-nulling micropressure system. The rate of formation of urine (derived by filtration of blood through the auricular wall) was measured using [⁵¹Cr] EDTA as a blood marker.Basal blood pressure was slightly above ambient (0.7 cm H₂O). Peak systolic pressure in the ventricle (3.8 cm H₂O) was synchronised with a subambient trough in pericardial pressure (–1.0 cm H₂O); these pressure pulses were out of phase with that of the auricle (2.3 cm H₂O) at systole. The observations are consistent in broad terms with a constant volume mechanism, but this does not take into account urine formation or filling of the nephridial gland vein.A filtration pressure of 1.5 cm H₂O has been demonstrated across the auricular wall throughout the cardiac cycle. Colloidal back pressure appears to be negligible. The mean rate of urine formation is 0.26 l g^–1 min^–1.     

A flexible method to align large numbers of biological sequences

Summary A method for the alignment of two or more biological sequences is described. The method is a direct extension of the method of Taylor (1987) incorporating a consensus sequence approach and allows considerable freedom in the control of the clustering of the sequences. At one extreme this is equivalent to the earlier method (Taylor 1987), whereas at the other, the clustering approaches the binary method of Feng and Doolittle (1987). Such freedom allows the program to be adapted to particular problems, which has the important advantage of resulting in considerable savings in computer time, allowing very large problems to be tackled. Besides a detailed analysis of the alignment of the cytochrome c superfamily, the clustering and alignment of the PIR sequence data bank (3500 sequences approx.) is described.     

A model for the generation of intra-uterine pressure in the human parturient uterus which demonstrates the critical role of the cervix

A mathematical model is presented which describes the relationship between intrauterine pressure and uterine wall tension. Wall tension is evaluated in terms of muscular contraction in an active myometrium and the modulating effect of a passive, compliant cervix. Using a computer programme which simulates the recruitment of contractile elements in the uterine wall, it is possible to generate theoretical pressure waveforms. The effects on these waveforms produced by changing cervical properties are demonstrated and compared with observed phenomena. The physiological and clinical implications are evaluated.     

Relation of changes in amount and type of dietary fat to fecapentaenes in premenopausal women

Correlation studies suggest that fecal mutagenicity is increased in groups eating high-fat diets, the same groups who are often found to have high colorectal cancer incidence and mortality. The fecapentaenes are the best characterized class of fecal mutagens, but the relationship of dietary fat intake to the excretion of these potent genotoxins is unknown. We studied the effect of changes in amount and type of dietary fat on fecapentaene levels in 31 premenopausal women 20-40 years of age who participated in a controlled feeding study. After a pre-diet free-living period lasting 1 menstrual cycle, women were placed on a high-fat (40% energy from fat) diet for 4 menstrual cycles and then switched to a low-fat (20% energy from fat) diet for an additional 4 menstrual cycles. One-half the subjects were maintained throughout the study at a ratio of polyunsaturated-to-saturated fatty acids (P/S ratio) of 1.0, the other half at 0.3; body weight was constant. All meals during the controlled diet periods were prepared at the Human Study Facility of the Beltsville Human Nutrition Research Center. Fecapentaene and fecapentaene precursor levels were measured in acetone extracts from 3-day pooled stool samples collected during the study. No differences in fecapentaene or precursor levels were observed between the high- and low-fat diets at either P/S ratio. Fecapentaene and precursor levels were higher while on controlled diets than during the pre-diet free-living period, and levels declined again in the post-diet free-living period. We conclude that dietary fat has no significant effect on fecapentaene or precursor levels in acetone extracts of stool in premenopausal women. The effect of other dietary or non-dietary factors on fecapentaenes remains unknown.