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Optimal concentrations of progesterone (P4) during early pregnancy are a major determinant of embryo survival in cattle. This study examined the effects of P4 supplementation, following a period of induced low P4, on corpus luteum (CL) development, circulating P4 concentrations and embryo development. A total of 107 beef heifers from one herd were used in the study. Following AI (Day 0) at a synchronized oestrus, heifers were randomly assigned to 1 of 5 treatment groups: (1) no subsequent treatment (control; n = 15); (2) administration of a synthetic prostaglandin F 2α analogue (PG ) on Days 3, 3.5 and 4 to induce low P4 and no further treatment (LP4; n = 23); administration of PG as above followed by P4 supplementation via insertion of a Controlled Internal Drug Release device from (3) Day 4–7 (P4 d4-7; n = 22); (4) Day 4–10 (P4 d4-10; n = 23); or (5) Day 7–10 (P4 d7-10; n = 24). Embryo and CL characteristics were determined following slaughter on Day 16. Embryo size was greater in heifers administered P4 d4-7 and P4 d4-10 in comparison with LP4. Corpus luteum area was significantly reduced in heifers administered P4 d4-7 and P4 d4-10 up to Day 7, and Day 10 (P4 d4-10), in comparison with LP4 heifers. Initiation of supplemental P4 on Day 7 had no effect on CL area or embryo size in comparison with LP4 heifers. Concentrations of P4 were less in P4 d4-7, P4 d7-10 and P4 d4-10 on Day 15 in comparison with LP4 heifers. The results of the study indicate an initiation and duration effect of supplemental P4 on circulating P4, embryo and CL development following induction of LP4 on Day 3 and 4. [ABSTRACT FROM AUTHOR]

This study investigated the factors affecting circulating progesterone (P4) concentrations in cows with similar genetic merit for milk production traits, but with extremes of good (Fert+) or poor (Fert-) genetic merit for fertility traits. Study 1: 28 cows were enrolled in an ovulation synchronization protocol at 61 ± 13 (±standard deviation) days postpartum, and data are presented for 13 Fert+ and 9 Fert- cows that remained in the study. Progesterone concentrations were determined from d 0 to 9 (d 0 = estrus) and on d 7, corpus luteum (CL) volume and blood flow area (BFA) were measured by B-mode and Doppler ultrasonography, respectively. Cows were administered PGF2α on d 7 in the p.m. and d 8 in the a.m. to regress the CL, and 2 controlled internal drug release devices were inserted per vaginum on d 8 in the a.m. Liver biopsies were collected on d 9 and hepatic mRNA abundance of genes involved in P4 catabolism was determined. On d 10, the controlled internal drug release inserts were removed and frequent blood samples were collected to measure the rate of decline in circulating P4. The Fert+ cows tended to have greater dry matter intake compared with Fert- cows (+0.79 kg of dry matter/d), but similar milk production (29.82 kg/d). After synchronized ovulation, the rate of increase in circulating P4 concentrations was greater in Fert+ cows compared with Fert- cows. No effect of genotype on CL volume was detected, but BFA was 42% greater in Fert+ cows compared with Fert- cows. The Fert- cows had greater mRNA abundance of cytochrome P450, family 3, subfamily A (CYP3A) compared with Fert+ cows, but the mRNA abundance of aldo-keto reductase family 1, member C1 (AKR1C1), AKR1C3, AKR1C4, and cytochrome P450, family 2, subfamily C (CYP2C) were similar. The half-life and metabolic clearance rate of P4 were similar in Fert+ cows and Fert- cows. Study 2: 23 cows were enrolled in an ovulation synchronization protocol at 55 ± 7 (±standard deviation) d postpartum, and data are presented for 13 Fert+ and 8 Fert- cows that remained in the study. On d 4, 7, 10, and 13 (d 0 = estrus), CL volume and BFA were measured as in study 1. Progesterone concentrations were measured from d 1 to 13. Corpus luteum volume was 41% greater in Fert+ cows compared with Fert- cows but no effect of genotype on BFA was detected. Mean circulating P4 concentrations were 79% greater in Fert+ cows compared with Fert- cows. Milk yield was similar in both genotypes. The results indicate that greater circulating P4 concentrations were primarily due to greater CL P4 synthetic capacity rather than differences in P4 clearance in this lactating cow genetic model of fertility. [ABSTRACT FROM AUTHOR]

The aim was to assess the ability of corpus luteum (CL) and uterine ultrasound characteristics on d 18 to 21 to predict pregnancy status in lactating dairy cows. Ultrasound examinations were carried out on cows (n = 164) on d 18 to 21 following artificial insemination (AI). Images of the uterus and CL were captured using a Voluson i ultrasound device (General Electric Healthcare Systems, Vienna, Austria) equipped with a 12-MHz, multi frequency, linear array probe. Serum concentrations of progesterone were determined from blood samples collected at each ultrasound examination. Images of the CL were captured and stored for calculation of CL tissue area and echotexture. Images of the CL and associated blood flow area were captured and stored for analysis of luteal blood flow ratio. Longitudinal B-mode images of the uterine horns were stored for analysis of echotexture. Diagnosis of pregnancy was made at each ultrasound examination based on CL blood flow, CL size, and uterine echotexture. Pregnancy was confirmed by ultrasonography on d 30 after AI. The relationship between ultrasound measures and pregnancy outcome, as well as the accuracy of the pregnancy diagnosis made at each ultrasound examination was assessed. Progesterone concentrations and CL tissue area were greater in pregnant compared with nonpregnant cows on all days. The CL blood flow ratio was higher in pregnant compared with nonpregnant cows on d 20 and 21 after AI. Echotexture measures of the CL and uterus were not different between pregnant and nonpregnant cows on any day of examination. The best logistic regression model to predict pregnancy included scores for CL blood flow, CL size, and uterine echotexture on d 21 following AI. Accuracy of pregnancy diagnosis was highest on d 21, with sensitivity and specificity being 97.6 and 97.5%, respectively. Uterine echotexture scores were similar for pregnant and nonpregnant cows from d 18 to 20. On d 21, pregnant cows had higher uterine echotexture scores compared with nonpregnant cows. The logistic regression equation most likely to provide a correct pregnancy diagnosis in lactating dairy cows included the visual score for CL blood flow, CL size, and uterine echotexture on d 21 after AI. In support of this finding, the diagnostic accuracy for visual scores of CL blood flow, CL size, and uterine echotexture were also highest on d 21. [ABSTRACT FROM AUTHOR]

Contents The objective was to examine the effect of lactation on uterine involution in post-partum dairy cows. Holstein primiparous cows were used (n = 19, mean age: 3.9 ± 0.1 years). At calving, cows were randomly assigned to one of two treatment groups, lactating (n = 11) or non-lactating (i.e. dried off at calving, n = 8). Examination of the reproductive tract was carried out by ultrasonography twice weekly until week 7 post-partum. Blood samples were collected twice weekly for the analysis of progesterone to indicate the resumption of cyclicity and metabolites indicative of energy status. Uterine involution was assessed in terms of size of the uterine horns, uterine body diameter and uterine fluid volume as assessed by the amount of non-echogenic material measured by ultrasound and position of the uterus. Vaginal mucous score was taken on day 28 post-partum for the assessment of uterine inflammation. Resumption of cyclicity (serum progesterone > 1 ng/ml) had occurred in both groups on average by day 21 post-partum. Concentrations of non-esterified fatty acids and beta-hydroxybutyrate were higher, whereas concentrations of glucose, insulin and IGF-1 were lower (p < 0.05) in lactating compared to non-lactating cows. Lactating cows had a smaller mean uterine body diameter (p < 0.05) than non-lactating cows from days 28 to 42 post-partum (day 28: 20.2 ± 1.3 vs 24.9 ± 1.5 mm, respectively) and had a lower mean uterine fluid volume up to day 49 (p < 0.05). By day 49, there was no difference in uterine diameter (15.2 ± 1.8 vs 15.2 ± 1.6 mm) or uterine fluid volume (0.11 ± 0.38 vs 0.18 ± 0.46) between lactating and non-lactating cows, respectively. Vaginal mucous score revealed no evidence of uterine inflammation in either group. In conclusion, while lactation induced significant alterations in metabolic status, it did not have a major effect on the rate of uterine involution as defined in this study. [ABSTRACT FROM AUTHOR]

With the worldwide increase in diabetes prevalence there is a pressing unmet need for novel antidiabetic therapies. Insufficient insulin production due to impaired β-cell function and apoptotic reduction of β-cell mass is a common denominator in the pathogenesis of diabetes. Current treatments are directed at improving insulin sensitivity, and stimulating insulin secretion or replacing the hormone, but do not target progressive apoptotic β-cell loss. Here we review the current development of small-molecule inhibitors designed to rescue β-cells from apoptosis. Several distinct classes of small molecules have been identified that protect β-cells from inflammatory, oxidative and/or metabolically induced apoptosis. Although none of these have yet reached the clinic, β-cell protective small molecules alone or in combination with current therapies provide exciting opportunities for the development of novel treatments for diabetes. [ABSTRACT FROM AUTHOR]

Abstract: A finite element methodology for thermo-mechanical fatigue analysis of a subcritical power plant outlet header under realistic loading conditions is presented. The methodology consists of (i) a transient heat transfer model, (ii) a sequential anisothermal cyclic viscoplastic model and (iii) a multiaxial, critical-plane implementation of the Ostergren fatigue indicator parameter. The methodology permits identification of the local thermo-mechanical stress–strain response at critical locations and prediction of fatigue life and cracking orientation for complex transient, anisothermal, cyclic elastic–plastic-creep material behaviour. Measured plant data, in the form of steam and pipe temperature transients and steam pressure data, are employed to identify heat transfer constants and validate the predicted thermal response, with particular attention given to plant start-up and attemperation effects. The predictions indicate out-of-phase temperature-strain response at the header inside surface and in-phase response on the outside surface. Cooling transients are predicted to control damage and crack initiation at the inner bore, whereas heating transients are predicted to have a more damaging effect at weld locations. A representative test cycle is presented, which is shown to capture the salient thermo-mechanical cyclic damage of the realistic cycle. The predicted results correlate well with industrial experience in terms of crack (initiation) orientation, location and life. [Copyright &y& Elsevier]

The aim of the present study was to test the hypothesis that elevated concentrations of progesterone (P4) resulting from the induction of an accessory corpus luteum (CL) by human chorionic gonadotrophin (hCG) administration on Day 5 after oestrus would lead to advanced conceptus elongation on Day 14 following embryo transfer on Day 7. The oestrous cycles of cross-bred beef heifers were synchronised and animals were randomly assigned to receive either of two treatments: (1) intramuscular injection of 3000 IU hCG on Day 5 after oestrus (n = 14); or (2) intramuscular injection of saline on Day 5 after oestrus (n = 13). Ovaries were scanned daily by transrectal ultrasonography to assess CL development. Serum concentrations of P4 were determined from daily blood samples collected from the jugular vein. In vitro-produced bovine blastocysts were transferred to synchronised recipients on Day 7 after oestrus (n = 15 blastocysts per recipient). Heifers were killed on Day 14 after oestrus and the uterus was flushed to recover the embryos. Injection of hCG on Day 5 induced ovulation of the dominant follicle in all treated heifers and increased the total area of luteal tissue on the ovary, which was associated with a significant increase (P < 0.001) in serum concentrations of P4 from Day 7 to Day 14. Positive associations were detected between circulating P4 with CL area (within-day correlations ranging from r = 0.45 to r = 0.67) and total area of luteal tissue (within-day correlations ranging from r = 0.65 to r = 0.86) Administration of hCG did not affect the proportion of Day 14 conceptuses recovered. However, compared with the control group, hCG-treated heifers had increased conceptus length (3.91 ± 1.23 vs 5.57 ± 1.02 mm, respectively; P = 0.06), width (1.00 ± 0.06 vs 1.45 ± 0.05 mm, respectively; P = 0.002) and area (5.71 ± 0.97 vs 8.31 ± 0.83, respectively; P = 0.02). Although numerically greater, mean interferon-τ (IFNT) production in vitro did not differ significantly (P = 0.54) between embryos recovered from hCG-treated and control heifers. In contrast, there was a strong positive correlation between individual embryo length (r = 0.76; P < 0.001) and individual embryo area (r = 0.72; P < 0.001) and IFNT production. In conclusion, administration of hCG on Day 5 after oestrus resulted in the formation of an accessory CL and hypertrophy of the original CL, the result of which was an increase in P4 concentrations from Day 7 onwards. These elevated P4 concentrations were associated with an increased conceptus area. Furthermore, conceptus size was highly correlated with IFNT secretion in vitro. Circulating progesterone concentrations during the first week after conception have been associated with increased pregnancy rates in cattle. In the present study, administration of human chorionic gonadotrophin on Day 5 after oestrus resulted in the formation of an accessory corpus luteum (CL) and hypertrophy of the original CL, the result of which was an increase in P4 concentrations from Day 7 onwards. These elevated P4 concentrations were associated with increased conceptus size. Furthermore, conceptus size was highly correlated with interferon-τ secretion in vitro. [ABSTRACT FROM AUTHOR]

Progesterone (P4) has a crucial impact on the transcriptome of the uterine endometrium and the preparation of the uterus to support implantation. The aim of this study was to investigate the effect of follicle aspiration just before ovulation on corpus luteum (CL) development, circulating P4 concentrations and the ability of the uterus to support embryo development and conceptus elongation. We tested the hypothesis that the unavoidable loss of follicular fluid and some granulosa cells during aspiration of the preovulatory follicle would compromise the development and function of the developing CL and that this would be associated with reduced P4 and a poorer uterine environment. Oestrous cycles of crossbred beef heifers were synchronized using an 8-day CIDR treatment with administration of a prostaglandin F2α analogue on the day before CIDR removal to ensure CL regression. Heifers were checked for signs of oestrus 4 times per day commencing 30 h after CIDR withdrawal and only those recorded in standing oestrus (Day 0, n = 20) were used. All heifers received a gonadotropin-releasing hormone agonist (0.01 mg buserelin) 48 h after CIDR removal to induce an LH surge. Half of the animals underwent follicle aspiration 20 h later, while the remainder underwent ovulation. Daily transrectal ultrasonography was carried out from Day 3 to 13 to record CL development. Daily blood samples were collected from Day 0 to 14 for circulating P4 concentrations. To test the ability of the uterus to support embryo development and conceptus elongation, Day 7 in vitro-produced blastocysts were transferred to the uteri of synchronised recipients (7 to 10 blastocysts per recipient). All recipients were slaughtered on Day 14 to assess embryo survival and conceptus size. CL diameter and CL area were significantly reduced in the follicle aspirated group compared with controls from Day 6 onwards (P ≤ 0.05). Similarly, at slaughter on Day 14, CL weight (4.17 ± 0.48 vs 7.05 ± 1.65 mm), diameter (19.89 ± 1.35 vs 24.64 ± 2.07 mm) and area (321.94 ± 45.01 vs 510.18 ± 69.41 mm2) were lower in aspirated heifers (P ≤ 0.05). Circulating P4 concentrations were lower at all time points from Day 3 to Day 14 but were only significantly lower from Day 12 onwards (P ≤ 0.05). Conceptus length (2.08 ± 0.29, n = 56 vs 4.55 ± 0.78 mm, n = 45) and area (2.52 ± 0.39 vs 5.61 ± 1.12 mm2) were lower (P ≤ 0.05) in heifers undergoing follicular aspiration compared with those undergoing ovulation. In conclusion, aspiration of the preovulatory dominant follicle just before expected ovulation was associated with a compromised CL in terms of size and P4 output and this, in turn, was associated with a reduced capacity of the uterus to support the initiation of conceptus elongation. Supported by Science Foundation Ireland (07/SRC/B1156). [ABSTRACT FROM AUTHOR]

Abstract: It has been established from (a) the tube thermal flux calculations, (b) the failure surface fractographic features, (c) the data sheets on evaporator tube temperatures from both Mitsubishi and Seimens, (d) the reported data from the literature and (e) to a certain extent, the tube strain gauge data that the recent waterwall tube failures in two 250MW boilers were the result of high stresses being active at certain boiler locations. At start-up these stresses were estimated from fractographic features to be around 370–420MPa in magnitude, which resided between the tube materials yield and ultimate tensile strengths. The defect extension process in the present waterwall tube failures was shown to be fatigue crack growth, which is the most common failure mode in waterwall boiler tubes. By adopting two separate approaches, viz., an “upper bound” ASME XI design line and an influence diagram model approach which was designed specifically for waterwall tubes, detailed remnant life values could be estimated for a number of different situations. In the case of new replacement tubes, both approaches estimated a remnant life of about 9 years. Note that the failure probability of the upper bound ASME XI predictions was demonstrated to be around 10−5. Also the influence diagram model approach was extremely helpful in identifying the probable root cause of corrosion fatigue failures in waterwall boiler tubes. With respect to the remnant life estimates two separate cases were considered, viz., (1) tubes with defect populations as recorded during the recent NDT study and (2) new replacement evaporator tubes which contained zero defects. [Copyright &y& Elsevier]

Ion pair formation, generically described as AB→A++B-, from vacuum-UV photoexcitation of trifluoromethyl sulfur pentafluoride, SF5CF3, has been studied by anion mass spectrometry using synchrotron radiation in the photon energy range of 10–35 eV. The anions F-, F2-, and SFx- (x=1–5) are observed. With the exception of SF5-, the anions observed show a linear dependence of signal with pressure, showing that they arise from ion pair formation. SF5- arises from dissociative electron attachment, following photoionization of SF5CF3 as the source of low-energy electrons. Cross sections for anion production are put on to an absolute scale by calibration of the signal strengths with those of F- from both SF6 and CF4. Quantum yields for anion production from SF5CF3, spanning the range of 10-7–10-4, are obtained using vacuum-UV absorption cross sections. Unlike SF6 and CF4, the quantum yield for F- production from SF5CF3 increases above the onset of photoionization. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the relationship between observed estrous-related behavior, activity clusters (AC; detected by automatic activity monitor), endocrine profiles, and ovulation time. Twenty-one cows in estrus (after 2 cloprostenol treatments, 11 d apart) and 12 nonsynchronized cows, to establish Heatime (SCR Engineers Ltd., Netanya, Israel) herd baseline activity, were enrolled. Cows had Heatime monitors applied 3 wk before the trial to establish their own baseline activity level. Cows in standing estrus had ultrasonography and phlebotomy carried out every 4 h to determine dominant follicle size, endocrine profiles, and ovulation time. After ovulation, these procedures were repeated once on d 3 to 6. Heatime alerted estrus in 90% of cows, and incorrectly alerted 17% of AC. The mean ± SEM duration for standing estrus was 9 ± 1 and 13 ± 1 h for estrous-related behavior. Estrous-related behavior began after the start of the proestrous estradiol-17β (E2) increase (59 ± 6.5 h). Cows with longer durations of raised proestrous E2 had longer intervals from its onset to the start of standing estrus and AC. The AC duration increased with longer durations of estrous-related behavior. Higher peak E2 occurred with longer standing estrus and estrous-related behavior. As E2 concentration decreased after the peak, 90% of cows still had estrous-related behavior. Duration of estrous-related behavior increased with higher average E2 concentration during the last 8 h before the start of the LH surge. During this surge 90% of cows had all of their standing estrus. As yields increased, so did the magnitude of the preovulatory FSH surges. Higher surges occurred with shorter standing estrus and estrous-related behavior. Cows with shorter LH surges had longer standing estrus. Peak LH preceded the AC peak (6.6 ± 0.8 h). Duration of overlap between the AC start and the LH surge end ranged between 0 and 14 h; 1 cow had none. No association was found between the AC characteristics with the E2, LH, or FSH profiles. In conclusion, the relationship between the timing of the E2 increase and estrous activity may be mediated by other factors (GnRH surge). Estrous-related behavior, but not endocrine profiles, was related to AC duration. Timing of standing estrus during the LH surge ensures that mating allows sperm maturation before ovulation. Based on the interval from the start of an AC to ovulation (27 ± 1 h), the optimum time to artificial insemination is, on average, between 9 and 15 h after the AC start. [ABSTRACT FROM AUTHOR]

Recent advances in the description of atoms and molecules based on Dimensional scaling analysis, developed by Dudley Herschbach and co-workers, provided new insights into visualization of molecular structure and chemical bonding. Prof. Herschbach is also a giant in the field of single molecule scattering. We here report on the engineering of molecular detectors. Such systems have a wide range of application from medical diagnostics to the monitoring of chemical, biological and environmental hazards. We discuss ways to identify preselected molecules, in particular, mycotoxin contaminants using coherent laser spectroscopy. Mycotoxin contaminants, e.g. aflatoxin B1 which is present in corn and peanuts, are usually analysed by time-consuming microscopic, chemical and biological assays. We present a new approach that derives from recent experiments in which molecules are prepared by one (or more) femtosecond laser(s) and probed by another set. We call this technique FAST CARS (femto second adaptive spectroscopic technique for coherent anti-Stokes Raman spectroscopy). We propose and analyse ways in which FAST CARS can be used to identify preselected molecules, e.g. aflatoxin, rapidly and economically. [ABSTRACT FROM AUTHOR]

Matrix remodeling, degradation, inflammation and invasion liberate peptide fragments that can subsequently interact with cells in an attachment-independent manner. Such ‘soluble’ matrix components, including collagens, fibronectin and laminin, induced Smad activation (termed crosstalk signaling), which follows a similar chronological sequence and R-Smad specificity as induced by transforming growth factor (TGF)-β1. Smad4 nuclear translocation occurred in response to collagen binding, indicating downstream signal propagation. TGF-β scavenging antibody affected only TGF-β1, but not crosstalk-induced responses. TGF-β type II receptor mutation (DR26Δ25), which is deficient in TGF-β type I receptor recruitment to the ligand, induced a heterotetramer signaling complex, and propagated Smad2 activation only through collagen induction and not TGF-β signaling. Consequentially, TGF-β ligand participation is not required for crosstalk signaling. This signaling requires a functional integrin β1 receptor as showed by RNA interference. Co-immunoprecipitation (co-IP) and fluorescent microscopy indicate the involvement of focal adhesion kinase (FAK) and Src activity in collagen-induced signal propagation, and suggest a membrane signaling complex formation that includes both TGF-β receptors and integrins. The related gene expressional responses are distinct from that evoked by TGF-β1, supporting its separate function. This signaling mechanism expands and partially explains TGF-β receptor dynamics and consequential signaling diversity-related gene expressional plasticity. [ABSTRACT FROM AUTHOR]

Abstract. The epithelium of the oral cavity and small intestine of the gastrointestinal tract have a high rate of cell renewal and as such, are sensitive to cytotoxic therapies that kill rapidly dividing cells. Mucositis is a complication of cancer therapy where impairment of the regenerative capacity of the epithelium leads to atrophy, ulceration and a loss of barrier function. Keratinocyte growth factor (KGF) is an epithelial cell-specific growth and differentiation factor that is trophic for the mucosal epithelium of the gastrointestinal tract. In this study, KGF in normal animals caused epithelial thickening in the squamous epithelium of the oral cavity and increased crypt depth and villus height of the small intestine. It also appeared to regulate gene expression in these tissues including that of some antioxidant enzymes and intestinal trefoil protein. KGF has been shown to be efficacious in several preclinical models of mucositis where KGF pretreatment reduced weight loss typically seen during and after the course of therapy and significantly improved survival. At a tissue level KGF reduced atrophy, accelerated regrowth, and decreased ulcer formation of the oral epithelium after irradiation, and improved crypt survival and prevented villus atrophy in the small intestine of irradiated or chemotherapy-treated mice. Preliminary studies suggest that its efficacy may be partly a consequence of the growth and differentiation effect, and also partly due to regulation of the expression of genes that play a role in mucosal protection. These data suggest that KGF may be useful for the prevention or treatment of mucositis in patients treated with regimens of cancer therapy that have gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

We prospectively evaluated whether delivering a thermal dose of ≥10 cumulative equivalent minutes at 43°C to >90% of the tumour sites monitored (CEM43° T[sub 90]) would produce a pathologic complete response (pCR) in ≥ 75% of high-grade soft tissue sarcomas treated pre-operatively with thermoradiotherapy. The impact of thermal dose on local failure (LF), distant metastasis (DM), and toxicity was also assessed. Thirty-five patients ≥ 18 years old with grade 2 or 3 soft tissue sarcomas accessible for invasive thermometry were enrolled on the protocol. All patients received megavoltage external beam radiotherapy (RT) in daily fractions of 1.8-2.0Gy, five times a week, to a median total dose of 50Gy and an initial hyperthermia treatment (HT) of 1h duration utilizing the BSD 2000 with Sigma 60 or MAPA applicators at frequencies of 60-140MHz. Further HT was given for patients with CEM43° T[sub 90] > 0.5 after initial HT ('heatable' patients), twice a week to a maximum of 10 HT or CEM43° T[sub 90] > 100. Of the 35 patients entered, 30 had heatable tumours, one of which was inevaluable for pCR or LF as the patient died of DM prior to surgery, leaving 29 evaluable patients. Of these 29 patients, 15 (52%) had a pCR (95% CI: 37-73%), significantly less than the projected rate of ≥75% (p = 0.02). Of the 25 heatable tumours that achieved CEM43° T[sub 90] ≥10, 14 (56% ) had a pCR (95% CI: 39-78%) significantly less than the projected rate (p = 0.06). Three of the 29 patients (10% ) with heatable tumours had a LF, versus 1/5 unheatable tumours (p = 0.48). Fourteen of the 30 patients (47%) with heatable tumours developed DM, versus 2/5 unheatable tumours (p = 1.00). Ten of the 30 patients (33%) with heatable tumours developed treatment-induced toxicity. Thus, no correlation of thermal dose with histologic response was observed. Prospective control of CEM43° T[sub 90] failed to achieve the projected pCR rate following pre-operative thermoradiotherapy for high-grade soft tissue sarcomas, despite excellent local control. Possible explanations for this outcome are discussed. [ABSTRACT FROM AUTHOR]

Osteoclast precursors (OCPs) circulate in the mononuclear fraction of peripheral blood (PB), but their abundance and surface characteristics are unknown. Previous studies suggest that the receptor activator for NF-κB (RANK) on cytokine-treated OCPs in mouse bone marrow interacts with osteoprotegerin ligand (OPGL/TRANCE/RANKL/ODF) to initiate osteoclast differentiation. Hence, we used a fluorescent form of human OPGL (Hu-OPGL-F) to identify possible RANK-expressing OCPs in untreated peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analysis. Monocytes [CD14-phycoerythrin (PE) antibody (Ab) positive (+) cells, 10–15% of PBMCs] all (98–100%) co-labelled with Hu-OPGL-F (n > 18). T lymphocytes (CD3-PE Ab+ cells, 66% of PBMCs) did not bind Hu-OPGL-F; however, B cells (CD19-PE Ab+ cells, 9% of PBMCs) were also positive for Hu-OPGL-F. All Hu-OPGL-F+ monocytes also co-labelled with CD33, CD61, CD11b, CD38, CD45 and CD54 Abs, but not CD34 or CD56 Abs. Hu-OPGL-F binding was dose dependent and competed with excess Hu-OPGL. When Hu-OPGL-F+, CD14-PE Ab+, CD33-PE Ab+, Hu-OPGL-F+/CD14-PE Ab+ or Hu-OPGL-F+/CD33-PE Ab+ cells were cultured with OPGL (20 ng/ml) and colony-stimulating factor (CSF)-1 (25 ng/ml), OC-like cells readily developed. Thus, all freshly isolated monocytes demonstrate displaceable Hu-OPGL-F binding, suggesting the presence of RANK on OCPs in PB; also, OCPs within a purified PB monocyte population form osteoclast-like cells in the complete absence of other cell types in OPGL and CSF-1 containing medium. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of keratinocyte growth factor (KGF) on the structure of the stratified squamous epithelium of the tongue, buccal mucosa and oesophagus of normal and irradiated mice. Materials and methods: Female BDF1 mice were exposed to total body irradiation from a caesium source. The irradiated mice and normal, unirradiated mice were injected with 5mg/kg per day KGF or vehicle. Thickness and proliferation in the epithelium were measured. Results: KGF caused epithelial thickening of the non-keratinized layers in oral epithelium in normal mice. It increased the number of nucleated layers and influenced differentiation of post-mitotic cells in the upper layers by increasing the size and number of keratohyalin granules, and the number of desmosomes. Single and fractionated doses of radiation caused inhibition of proliferation as detected by markedly reduced BrdU incorporation following exposure, followed by epithelial atrophy. KGF treatment of mice reversed the inhibition of proliferation and atrophy that occurred in control irradiated mice. Conclusion: These data show that KGF reverses epithelial atrophy in mouse oral cavity caused by irradiation and suggest that KGF may be useful for the treatment of mucositis of the upper aerodigestive tract of patients treated with aggressive regimens of radiation therapy. [ABSTRACT FROM AUTHOR]

Examines osteoprotegerin (OPG) ligand, a cytokine that regulates osteoclast differentiation and activation. Identification of biologically active domain of OPG; Details on the pattern of OPGL in embryonic and adult mouse tissues; Information on OPGL administration bone stimulation in mice.

Absolute cross sections for the K-shell photoionization of Be-like boron ions were measured with the ion–photon merged-beams technique at the Advanced Light Source synchrotron radiation facility. High-resolution spectroscopy with E/ΔE up to 8800 (ΔE ∼ 22 meV) covered the energy ranges 193.7–194.7 eV and 209–215 eV. Lifetimes of the strongest resonances are determined with relative uncertainties down to approximately 4% for the broadest resonance. The measured resonance strengths are consistent with 60% 1s22s2 1S ground-state and 40% 1s22s2p 3Po metastable-state ions in the primary ion beam and confirmed by comparison with independent absolute photo-recombination heavy-ion storage-ring measurements with B2 + ions using the principle of detailed balance. Experimental determination of the line width for the 1s2s22p 1Po resonance gives a value of 47 ± 2 meV and compares favourably to a theoretical estimate of 47 meV from the R-matrix with pseudo-states (RMPS) method. The measured line widths of the 1s2s2p23P, 3D resonances are 10.0 ± 2 meV and 32 ± 3 meV, respectively, compared to RMPS theoretical estimates of 9 meV and 34 meV. [ABSTRACT FROM AUTHOR]