Is body mass index before middle age related to coronary heart disease risk in later life? Evidence from observational studies.

OBJECTIVE: Although obesity beginning early in life is becoming more common, its implications for coronary heart disease (CHD) risk in later life remain uncertain. We examined the relationship of body mass index (BMI) before 30 years of age to CHD risk in later life. DESIGN: Systematic review of published studies relating BMI between age 2 and 30 years to later CHD risk. Studies were identified using Medline (1950 onwards), Embase (1980 onwards) and Web of Science (1970 onwards) databases (to November 2007). MEASUREMENTS: Relative risks (RR) of CHD associated with a 1 standard deviation (s.d.) higher BMI (most based on a narrow age range at measurement) were extracted by two authors independently, and combined using random-effect models. RESULTS: A total of 15 studies provided 17 estimates (731 337 participants, 23 894 CHD events) of the association of early BMI to later CHD outcome. BMI in early childhood (2-6 years, 3 estimates) showed a weak inverse association with CHD risk (RR 0.94, 95% CI 0.82-1.07). BMI in later childhood (7 to <18 years, 7 estimates) and BMI in early adult life (18-30 years, 7 estimates) were both positively related to later CHD risk (RR 1.09, 95% CI 1.00-1.20; RR 1.19, 95% CI 1.11-1.29 respectively). However, there was considerable statistical heterogeneity between study estimates. Results were unaffected by adjustment for social class and/or cigarette smoking, blood pressure and/or total cholesterol, in studies with available data. Gender and year of birth (1900-1976) had little effect on the association. CONCLUSIONS: BMI is positively related to CHD risk from childhood onwards; the associations in young adults are consistent with those observed in middle age. Long-term control of BMI from childhood may be important to reduce the risk of CHD.

A structured system to evaluate urethral support anatomy in magnetic resonance images.

OBJECTIVE: To develop a systematic method for analyzing the normal magnetic resonance imaging location and appearance of structural features involved in urethral support. STUDY DESIGN: Multiplanar proton density magnetic resonance images of 50 nulliparous women were made at 0.5-cm intervals. The arcuate pubic ligament was the chosen reference point in all views. Structural features were located by identification of the magnetic resonance images in which they appeared. The presence or absence of urethral support structures in each scan level relative to the arcuate pubic ligament was evaluated and recorded as a graphic display. Support structures examined were the arcus tendineus fasciae pelvis, the perineal membrane, the pubococcygeal levator ani muscle and its vaginal and bony attachments, and the pubovesical muscle. Structural definitions were developed on the basis of established periurethral anatomy. Two examiners independently assessed 10 scans for interobserver concordance. This system was used in nulliparous women to quantify the location of magnetic resonance visible structures. RESULTS: Because all levels were 0.5 cm apart, slice identification represented the distance above the arcuate pubic ligament (eg, 2 images above the arcuate pubic ligament or 1.0 cm). Interobserver concordance was 88% in identification of structure location. In the axial plane, specific structural features and relationships were localized. The frequency at which a specific structure was observed at a specific image level in all women was depicted as a gray density within the graphic display. These frequencies indicated where we would expect each structure to be located in healthy women. Relationships between structures and their attachments became apparent. Consideration of expected structural locations proven by nulliparous scans will enable us to quantitatively define abnormal structures in parous women. CONCLUSIONS: This systematic magnetic resonance evaluation allows, for the first time, quantification of the normal anatomic location of urethral support structures. It can be used to help identify the difference between structural abnormalities and normal variation in parous women.

Clinical presentation of enterocele.

OBJECTIVE: To characterize preoperative signs and symptoms in women with and without enteroceles. METHODS: Three hundred ten women completed preoperative questionnaires and had prolapses graded according to the International Continence Society system. Signs and symptoms in 77 women (25%) with enteroceles confirmed at surgery were compared with those in 233 women without enteroceles. Comparisons were tested for statistical significance with chi(2) tests, Fisher exact tests, Wilcoxon rank-sum tests, and analysis of covariance. RESULTS: Women with enteroceles were statistically significantly older (median 67 versus 59 years, P <.001) and more likely to be postmenopausal (88% versus 76%, P =.04). More women with enteroceles had histories of hysterectomies (76% versus 39%, P =.001) and vaginal prolapse repairs (24% versus 11%, P =.008). Women with enteroceles had more advanced prolapses at points Ap, Bp, and C (all P <.001) but not point D. There were no significant differences in symptoms related to bowel function (infrequent bowel movements, straining, manual evacuation, and fecal incontinence) in women with and without enteroceles. Women with enteroceles were more bothered by symptoms caused by vaginal prolapse than women without enteroceles, but not after we controlled for stage of prolapse. CONCLUSION: Women with enteroceles have more advanced apical and posterior vaginal prolapses than women without enteroceles, but do not differ from them in bowel function.

Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression.

Recently we reported that, in HL-60 cells, transcription of the formyl peptide receptor (FPR) gene can be up- and downregulated by agents that induce differentiation of HL-60 cells into neutrophils. To begin studying the mechanisms involved in regulation of FPR gene expression, we cloned two human cDNAs and the gene coding for FPR. The genomic clone (pINF14) contained a 14.5-kb insert. A 2.7-kb EcoRI fragment was obtained from pINF14 that hybridized with an FPR open reading frame probe. The EcoRI fragment was sequenced and found to contain an intronless FPR open reading frame. Sequence alignment of the EcoRI genomic fragment with the FPR cDNA revealed that the first 31 bases of 5' untranslated FPR cDNA were not represented in the genomic fragment. Furthermore, a splicing consensus sequence was present in the genomic fragment at the site of divergence with the cDNA sequence. Restriction mapping and Southern blot analysis identified a 121-bp fragment that contained the sequence corresponding to the first 31 bases of 5' untranslated FPR cDNA. An additional (previously undescribed) 15-bp cDNA sequence in the 5' end of FPR were identified using an anchored polymerase chain reaction. This sequence was also contained in the genomic 121-bp fragment. This 121-bp fragment was located 5.2 kb (intron) upstream of the FPR open reading frame. It contained an unusual TATA box and displayed transcriptional activity in vitro and in vivo. Potential binding sites for AP-1 and glucocorticoid receptor were identified upstream of the putative TATA box.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of pre-PCR mis-priming and primer dimerization improves low-copy-number amplifications.

A Hot Start Polymerase Chain Reaction (PCR) entails the withholding of at least one reagent from the reaction mixture until the reaction tube temperature has reached 60-80 degrees C. Hot Start amplification with an AmpliWax vapor barrier uses a layer of solid wax to separate the retained reagent(s) and the test sample from the bulk of the reagents until the first heating step of automated thermal cycling melts the wax and convectively mixes the two aqueous layers. Wax-mediated Hot Start PCR greatly increases the specificity, yield, and precision of amplifying low copy numbers of three HIV targets. In the presence of 1 microgram of human placental DNA (1.6 x 10(5) diploid genomes) the specificity improvement entails considerable to complete reduction in the amplification of mis-primed sequences and putative primer oligomers. When mis-priming is negligible, the procedural improvement still suppresses putative primer oligomerization. Hot Start PCR with an AmpliWax vapor barrier permits routine amplification of a single target molecule with detection by ethidium stained gel electrophoresis; nonisotopically visualized probing suffices for confirmation. The improved amplification performance is evident for target copy numbers below approximately 10(3).

Purification and characterization of fructose-2,6-bisphosphatase, a substrate-specific cytosolic enzyme from leaves.

Fructose-2,6-bisphosphatase (EC 3.1.3.46), which hydrolyzes fructose 2,6-bisphosphate to fructose 6-phosphate and Pi, has been purified to apparent homogeneity from spinach leaves and found to be devoid of fructose-6-phosphate,2-kinase activity. The isolated enzyme is a dimer (76 kDa determined by gel filtration) composed of two 33-kDa subunits. The enzyme is highly specific and displays hyperbolic kinetics with its fructose 2,6-bisphosphate substrate (Km = 32 microM). The products of the reaction, fructose 6-phosphate and Pi, along with AMP and Mg2+ are inhibitors of the enzyme. Nonaqueous cell fractionation revealed that, like the fructose 2,6-bisphosphate substrate, fructose-2,6-bisphosphatase as well as fructose-6-phosphate,2-kinase occur in the cytosol of spinach leaves.

Activities synthesizing and degrading fructose 2,6-bisphosphate in spinach leaves reside on different proteins.

Activities catalyzing the synthesis and degradation of fructose 2,6-bisphosphate-6-phosphofructo-2-kinase (ATP:D-fructose-6-phosphate-2-phosphotransferase, EC 2.7.1.105) and fructose-2,6-bisphosphatase (D-fructose-2,6-bisphosphate 2-phosphohydrolase, EC 3.1.3.46)-were isolated from spinach leaves by an improved procedure and separated on the basis of both charge and molecular weight. The separated activities showed no detectable cross-contamination, indicating, in contrast to all previous data, that they are not present on a single bifunctional protein of the classical type in liver. The fructose-2,6-bisphosphatase-a newly discovered phosphatase enzyme-differed from previous mixed preparations by showing greater specificity but lower affinity for fructose 2,6-bisphosphate, greater sensitivity to inhibition by inorganic phosphate, and in being sensitive to inhibition by Mg(2+). The 6-phosphofructo-2-kinase was found to be inhibited by low levels of inorganic pyrophosphate and, in addition, to be regulated by the metabolites described previously. Similar results were obtained with preparations from lettuce leaves. The results support the view that, through individual regulation of the activities catalyzing its synthesis and breakdown, cytosolic metabolites are key factors in controlling the fructose 2,6-bisphosphate content of leaves.

Ion-exchange chromatography separates activities synthesizing and degrading fructose 2,6-bisphosphate from C3 and C4 leaves but not from rat liver.

Fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase were separated on the basis of charge from leaves of C3 (spinach, lettuce, and pea) and C4 (sorghum and amaranthus) plants but not from rat liver--a tissue known to contain a bifunctional enzyme with both activities. [2-32P]Fructose 2,6-bisphosphate binding experiments also suggest that the major forms of these activities reside on different proteins in leaves.