Observation of picometer vertical emittance with a vertical undulator.

Using a vertical undulator, picometer vertical electron beam emittances have been observed at the Australian Synchrotron storage ring. An APPLE-II type undulator was phased to produce a horizontal magnetic field, which creates a synchrotron radiation field that is very sensitive to the vertical electron beam emittance. The measured ratios of undulator spectral peak heights are evaluated by fitting to simulations of the apparatus. With this apparatus immediately available at most existing electron and positron storage rings, we find this to be an appropriate and novel vertical emittance diagnostic.

Evidence for direct CP violation in B0-->K+pi- decays.

We report evidence for direct CP violation in the decay B0-->K+pi(-) with 253 fb(-1) of data collected with the Belle detector at the KEKB e(+)e(-) collider. Using 275x10(6) BB pairs we observe a B-->K+/-pi(-/+) signal with 2140+/-53 events. The measured CP violating asymmetry is A(CP)(K+pi(-))=-0.101+/-0.025(stat)+/-0.005(syst), corresponding to a significance of 3.9sigma including systematics. We also search for CP violation in the decays B+-->K+pi(0) and B+-->pi(+)pi(0). The measured CP violating asymmetries are A(CP)(K+pi(0))=0.04+/-0.05(stat)+/-0.02(syst) and A(CP)(pi(+)pi(0))=-0.02+/-0.10(stat)+/-0.01(syst), corresponding to the intervals -0.05

Evidence for B0-->rho0pi0.

We present the first evidence of the decay B0-->rho(0)pi(0), using 140 fb(-1) of data collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. We detect 15.1+/-4.8 signal events with a significance of 3.5 standard deviations and measure the branching fraction to be B(B0-->rho(0)pi(0))=(5.1+/-1.6(stat)+/-0.9(syst))x10(-6).

Impaired mammary function and parathyroid hormone-related protein during lactation in growth-restricted spontaneously hypertensive rats.

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) during lactation, including stimulation of mammary and pup growth. As spontaneously hypertensive rat (SHR) pups are growth restricted compared with the control Wistar Kyoto (WKY), we examined the relative roles of pup suckling and maternal lactational environment on pup growth, mammary PTHrP, and milk PTHrP and calcium concentrations. SHR pups were lighter compared with the control from 6 days. SHR mammary PTHrP content and milk PTHrP were lower but maternal plasma PTHrP was raised compared with WKY. SHR mammary morphological development was also impaired compared with control. Cross fostering growth-restricted pups onto WKY mothers increased pup weight in association with normal mammary function and higher milk PTHrP and calcium. Control pups suckling on an SHR mother had reduced body weight. Both cross fostering groups were associated with increased maternal and milk PTHrP concentrations, indicating the importance of suckling, together with a functional mammary gland. The results suggested that impaired SHR mammary function and milk PTHrP are associated with a reduced SHR postnatal growth. Our data also indicated that milk and mammary PTHrP are regulated by different mechanisms but that they are influenced by the maternal lactational environment and the suckling pup.

Role of calcium, vitamin D, and other essential nutrients in the prevention and treatment of osteoporosis.

Calcium is an essential nutrient for the prevention and treatment of osteoporosis. Despite universal recognition of its importance, most people still do not obtain recommended amounts. Recent additions to the treatment of osteoporosis with potent bone active drugs produce an even greater need for calcium and total nutrition for restoration of lost bone. Practitioners and patients need to emphasize and appreciate the role that calcium, vitamin D, and other nutrients play in the promotion of health and in the prevention and treatment of disease.

Study subjects and ordinary patients.

Clinical trials of treatment agents impose strict and often necessary inclusion and exclusion criteria, while patients presenting to physicians for treatment frequently exhibit complicating features that would have excluded them from entry into study. To quantify the degree of discordance between ordinary patients and study subjects, a retrospective chart review was carried out of all new patients with osteoporosis seen in an academic medical center within a consecutive 40-month period, meeting clinical treatment criteria. Each patient chart was reviewed for the inclusion and exclusion criteria of four large, multicenter study protocols. There were 120 consecutive female patients seeking health care, with bone density T-scores below -2.0 and/or with one or more low-trauma fractures. The four trials would have accepted 4, 5, 25 and 8 of our 120 patients. The trial with the most liberal inclusion criteria would have taken only 21% of the total. Principal reasons for ineligibility were comorbidity, prior treatment with bone-active agents, and current therapy with glucocorticoids, anticoagulants and anticonvulsants. Some of these exclusions inevitably reflect the patient mix of a referral center; nevertheless, comorbidity and its therapy are common in the age range in which osteoporosis is prevalent and would, therefore, be expected to be present in patients in general medical practice as well. Thus a large fraction, perhaps the majority, of patients with diagnoses of osteoporosis who are candidates for treatment by their physicians, are not eligible for entry into typical treatment trials. The results of such trials may, therefore, have uncertain applicability to types of patients excluded, both for safety and for efficacy.

Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women.

Several lines of evidence suggest the importance of the estrogen receptor (ER) in determining body mass index (BMI). Our purpose was to investigate whether genetic polymorphisms at the restriction enzyme PvuII site of the ER-alpha gene locus are associated with BMI variation. Data on BMI, age, and ER-alpha genotypes were obtained from 108 healthy midwestern U.S. postmenopausal Caucasian women. The study subjects were unrelated and aged 65 yr and over (mean age +/- SD, 73.4 +/- 5.1 yr), with an average BMI of 25.25 (SD, 4.04). The ER-alpha genotypes were obtained by PCR followed by restriction enzyme PvuII digestion. We found that in our study subjects the ER-alpha genotypes are significantly associated with BMI (by ANOVA, P = 0.04), explaining about 6.2% of the BMI variation in our study sample. The allelic effects of this locus on BMI are approximately additive. In our sample, individuals of the PP and Pp genotypes have, respectively, 11.4% and 4.8% higher BMI than individuals of the pp genotype. There is a significant ER-alpha genotype by age interaction, so that in our sample PP individuals tend to gain weight with age, whereas Pp and pp individuals tend to lose weight with age. Therefore, the ER-alpha polymorphisms are associated with BMI variation in healthy postmenopausal Caucasian women aged 65 yr and over. Our result is consistent with some recent findings suggesting the potential effects of the ER on BMI. The importance of the ER-alpha genotypes in other populations and other age groups needs to be demonstrated. Although the results of the ER-alpha genotype by age interaction are obtained here from cross-sectional data, direct confirmation may come from longitudinal studies in which individuals are measured multiple times over several years. The importance of the ER-alpha genotypes on BMI should be confirmed by further studies using methods robust to the potential problem of population substructuring that may confound the conclusions of population association studies.

Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice.

INCENP is a chromosomal passenger protein which relocates from the centromere to thel spindle midzone during the metaphase-anaphase transition, ultimately being discarded in the cell midbody at the completion of cytokinesis. Using homologous recombination, we have generated Incenp gene-targeted heterozygous mice that are phenotypically indistinguishable from their wild-type littermates. Intercrossing the hetero-zygotes results in no live-born homozygous Incenp -disrupted progeny, indicating an early lethality. Day 3.5 affected pre-implantation embryos contain large, morphologically abnormal cells that fail to fully develop a blastocoel cavity or thrive in utero and in culture. Chromatin and tubulin immunocytochemical stainings of these and day 2.5 affected embryos reveal a high mitotic index, no discernible metaphase or anaphase stages, complete absence of midbodies, micronuclei formation, morphologically irregular macronuclei with large chromosome complements, multipolar mitotic configurations, binucleated cells, internuclear bridges and abnormal spindle bundling. The phenotype is consistent with a defect in the modulation of microtubule dynamics, severely affecting chromosome segregation and resulting in poorly resolved chromatin masses, aberrant karyokinesis and internuclear bridge formation. These latter occurrences could pose a physical barrier blocking cytokinesis.

The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.

BACKGROUND: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women. OBJECTIVE: To determine the bone-sparing effect of continuous low-dose HRT in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University osteoporosis research and clinical center. PATIENTS: 128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less. INTERVENTION: Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups. MEASUREMENTS: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months. RESULTS: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived. CONCLUSIONS: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.

Patient care of osteoporosis.

Osteoporosis is a condition of excessive skeletal fragility that afflicts more than 25 million Americans and results in over one half million fractures per year in the United States. Evaluation of patients presenting with symptoms of osteoporosis includes measurement of serum 25 hydroxy, vitamin D, thyroxine, thyroid-stimulating hormone, serum protein electrophoresis, in addition to blood count, urinalysis, and multichannel screen. Spine and other films are indicated as necessary, and although bone density measurements are useful, they are somewhat restricted in availability. There are lifestyle measures that influence the cause as well as the treatment of osteoporosis. Symptomatic patients benefit most by interventions that include nutrition, physical fitness, calcium, and vitamin D.

Hemisphere asymmetry and the processing of emotional words in anxiety.

High- and low-trait anxious subjects participated in a divided visual field emotional Stroop task. Subjects identified the colour of unilaterally presented threat-related, positive and neutral words. The high- and low-trait groups differed in terms of their accuracy scores but not in their reaction times. Analysis of the accuracy data revealed that the high-trait group exhibited right hemisphere interference for emotional relative to neutral trials whereas the low-trait showed right hemisphere interference for threat-related trials only. The idea that the right hemisphere is differentially specialised for the processing of emotional information was supported.

An unusual variant of blood group A.

A blood specimen from a forensic science case appeared to violate Landsteiner's Rule. The red cells failed to react with anti-A, anti-B, or O serum while reacting strongly with Ulex europaeus lectin but not other anti-A lectins. The saliva from the person involved was found to contain both A and H blood group substances in a ratio of 4:1. The blood group was determined to be type Am.