Biomedical subjects

R Webb

Publications and source records attributed to R Webb.

At least 37 records · Page 2Linked to original sources

PubMed2001

Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern.

AIMS: Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern. METHODS AND RESULTS: Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H). CONCLUSIONS: Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.

Biomarkers↗

PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗

PubMed2001

The role of leptin in the transition from fetus to neonate.

Leptin is a 16 kDa hormone which has been shown to have a major physiological role in the control of energy balance. Leptin is produced primarily in white adipose tissue, although there is evidence for its production in brown adipose tissue (BAT) and the placenta. BAT is critically important for the initiation of non-shivering thermogenesis in the newborn through the BAT-specific uncoupling protein (UCP), UCPI. This factor is particularly important in lambs in which levels of UCP1 peak at birth, concomitant with a rapid decline in plasma leptin levels. Our studies have examined the effect of acute and chronic administration of leptin to neonatal lambs, investigating effects on colonic temperature, UCP1 and thermogenic potential of BAT. Administration of leptin in sequential physiological doses of 10, 100 and 100 microg to neonatal lambs caused a modest increase in colonic temperature which was not observed in weight-matched vehicle-treated controls. This increase in colonic temperature was not mediated by an increase in either abundance or thermogenic potential of UCPI, as previously shown in adult rodents. UCP1 mRNA levels were 30 % lower in leptin-treated lambs, which is also contradictory to findings in adult rodents. Leptin treatment resulted in a dose-dependent rise in plasma leptin, with levels at the end of the study being almost twenty times greater in leptin-treated animals. To determine whether these findings in neonatal lambs were transient due to the complex milieu of hormones present after birth, we examined the effect of chronic leptin treatment over 6 d. Pairs of lambs were treated daily, from the second to seventh day of life with 100 microg leptin or vehicle. Colonic temperatures of leptin- and vehicle-treated animals remained similar throughout the study. UCP1 abundance was significantly lower in the leptin-treated animals, suggesting that the drop in UCP1 mRNA seen in the previous study had been translated to protein levels. In conclusion, the decline in plasma leptin levels at birth may be a signal to initiate enteral feeding. In lambs, the rapid loss of UCP1 mRNA, which occurs within the first few days of life, appears to be accelerated by leptin administration, possibly stimulating the development of white adipose tissue and generation of body heat through mechanisms other than non-shivering thermogenesis by UCP1 in BAT.

Adipose Tissue, Brown↗

PubMed2001

Protecting cotton photosynthesis during moderate chilling at high light intensity by increasing chloroplastic antioxidant enzyme activity.

This study examined the effect of increasing chloroplastic superoxide dismutase (SOD), ascorbate peroxidase (APX), or glutathione reductase (GR) activity via plant transformation of cotton on the initial recovery of photosynthesis following exposures to 10 degrees C and high photon flux density (PFD). Growing wild-type or non-expressing segregate plants (controls) and transformants at two PFDs (600 micromol m(-2) s(-1) and full sun) resulted in a range of total antioxidant enzyme activities. Total SOD activities above that for control leaves grown in full sun did not substantially improve the recoveries of CO(2)-saturated photosynthesis, especially for stress treatments lasting more than 1 h, while elevated APX or GR activity did improve recoveries after 1-3 h of the chilling treatment. No synergistic effects were noted when the activities of more than one antioxidant enzyme were elevated in transgenic hybrids. Although these results suggest that the protection of photosynthesis can be realized by reducing either superoxide or H(2)O(2) levels, thereby reducing the possibility of hydroxyl radical formation, the situation is complicated, since elevated APX or GR activity can improve recoveries even when additional SOD activity has no effect. In conclusion, to enhance the protection of photosynthesis using stroma-targeted antioxidant enzymes, enhancing metabolism associated with H(2)O(2) is more effective than enhancing the capacity for superoxide scavenging. Although small, the improvement in the protection of photosynthetic capacity may be sufficient to improve cotton yield in temperate regions with large diurnal temperature fluctuations.

Antioxidants↗

PubMed2001

Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro: associations with the ovarian insulin-like growth factor system.

Heifers were assigned either low or high (HE) levels of energy intake and low or high concentrations of dietary crude protein. The effect of these diets on the plasma concentrations of insulin, insulin-like growth factor (IGF)-I, and urea on follicular growth and early embryo development is described. We propose that the observed dietary-induced changes in the ovarian IGF system increase bioavailability of intrafollicular IGF, thus increasing the sensitivity of follicles to FSH. These changes, in combination with increased peripheral concentrations of insulin and IGF-I in heifers offered the HE diet, contribute to the observed increase in growth rate of the dominant follicle. In contrast to follicular growth, increased nutrient supply decreased oocyte quality, due in part to increased plasma urea concentrations. Clearly a number of mechanisms are involved in mediating the effects of dietary energy and protein on ovarian function, and the formulation of diets designed to optimize cattle fertility must consider the divergent effects of nutrient supply on follicular growth and oocyte quality.

Animals↗

PubMed2000

Search for new particles decaying to t&tmacr; in p&pmacr; collisions at radicals = 1.8 TeV

We use 106 pb (-1) of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an antitop quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to t&tmacr; are presented. At the 95% confidence level, we exclude the existence of a leptophobic Z' boson in a model of top-color-assisted technicolor with mass M(Z')<480 GeV/c(2) for natural width gamma = 0.012M(Z'), and M(Z')<780 GeV/c(2) for gamma = 0.04M(Z').

Journal Article↗

PubMed2000

Limits on light gravitino production and new processes with large missing transverse energy in p&pmacr; collisions at sqrt

Events collected by the Collider Detector at Fermilab (CDF) with an energetic jet plus large missing transverse energy can be used to search for physics beyond the standard model. We see no deviations from the expected backgrounds and set upper limits on the production of new processes. We consider in addition the production of light gravitinos and set a limit at 95% confidence level on the breaking scale sqrt[F]>/=217 GeV, which excludes gravitino masses smaller than 1.1x10(-5) eV/c(2).

Journal Article↗

PubMed2000

Description of a presumptive hepatopancreatic reovirus, and a putative gill parvovirus, in the freshwater crayfish Cherax quadricarinatus.

The redclaw freshwater crayfish Cherax quadricarinatus has a reputation for being hardy and resistant to handling stress. However, in recent years, possibly since 1996, C. quadricarinatus farmers in northern Queensland have noted a decrease in stress resistance in their stock. A presumptive reovirus in the hepatopancreas, and a putative parvovirus in the gills, were associated with chronic mortalities in C. quadricarinatus at one northern Queensland farm. Hypertrophic nuclei with marginated chromatin were observed in gill epithelium in moribund crayfish which had recently been relocated to a laboratory from the holding tank facility on the farm. Affected nuclei appeared to be vacant or contained a faint granular basophilia in H&E stained sections. However, toluidine blue staining revealed a homogeneously granular appearance of the nuclei. Transmission electron microscopy revealed approximately 20 nm diameter virus-like particles within the nucleus. Eosinophilic, Feulgen-negative, cytoplasmic inclusions were observed in distal hepatopancreatocytes in 1 moribund C. quadricarinatus collected from the same on-farm holding tank approximately 6 mo later. This crayfish did not display the gill lesions. Transmission electron microscopy showed that the inclusions contained icosahedral virus particles 35 to 40 nm in diameter. The histopathology and preliminary virus morphology of the presumptive hepatopancreatic reovirus, and the histopathology, ultrastructural pathology and preliminary virus morphology of the putative gill parvovirus, are reported herein.

Animals↗

PubMed2000

Diffractive dijets with a leading antiproton in &pmacr;p collisions at sqrt

We report results from a study of events with a leading antiproton of beam momentum fraction 0.905 7 GeV. Using the dijet events, we evaluate the diffractive structure function of the antiproton and compare it with expectations based on results obtained in diffractive deep inelastic scattering experiments at the DESY ep collider HERA.

Journal Article↗

PubMed2000

Ovarian autografts in sheep as a model for studying folliculogenesis.

The studies outlined in this review indicate that the cortical autograft, in addition to its clinical application as a means to restore fertility, represents a valuable experimental model that can be exploited to examine aspects of both early and terminal follicle development. The autograft procedure is a means to experimentally deplete the follicle population in an individual and this procedure results in similar endocrine changes and reproductive cycle perturbances as those observed in aged sheep and women with incipient ovarian failure. This methodology therefore represents a non-primate large animal model to study the consequences of, and possible interventions to overcome, reproductive problems associated with depleted ovarian follicular reserves. Without the necessity of keeping animals for large periods of time so that this depletion can occur naturally. In terms of early follicle development, the fact that the ischaemia that occurs during revascularisation of the autograft effectively synchronises follicle development at the primordial stages of development means that the autograft can be used as a model to study the control of early follicle development. This model has been used to examine the role of FSH (follicle stimulating hormone) in the control of early follicle development and the preliminary data presented provides strong evidence that FSH does indeed modulate early folliculogenesis, confirming the value of this model as a means of performing experimental investigations in this area. Further work using this model will concentrate on the role of other endocrine and local factors in the control of early folliculogenesis and the identification of the key developmental checkpoints during this process, with a view to designing physiological culture systems to support early follicle and oocyte development.

Animals↗

PubMed2000

Production of Upsilon(1S) mesons from chi(b) decays in p&pmacr; collisions at sqrt

We have reconstructed the radiative decays chi(b)(1P)-->Upsilon(1S)gamma and chi(b)(2P)-->Upsilon(1S)gamma in p&pmacr; collisions at sqrt[s] = 1.8 TeV, and measured the fraction of Upsilon(1S) mesons that originate from these decays. For Upsilon(1S) mesons with p(Upsilon)(T)>8.0 GeV/c, the fractions that come from chi(b)(1P) and chi(b)(2P) decays are [27.1+/-6.9(stat)+/-4. 4(syst)]% and [10.5+/-4.4(stat)+/-1.4(syst)]%, respectively. We have derived the fraction of directly produced Upsilon(1S) mesons to be [50.9+/-8.2(stat)+/-9.0(syst)]%.

Journal Article↗

PubMed2000

Nonglacial rapid climate events: past and future.

The paleoclimate record makes it clear that rapid climate shifts of the 20th century are only a subset of possible climate system behavior that might occur in the absence of glacial conditions, and that climatic surprises could be a challenge for society even in the absence of significant greenhouse warming.

Animals↗

PubMed2000

Monodon baculovirus from Australia: ultrastructural observations.

The cytopathology, virogenesis and replication of monodon baculovirus (MBV) in Penaeus monodon from Australia are described. Electron-dense unenveloped nucleocapsids, not previously described for MBV, are shown in the cytoplasm and attached to the nuclear envelope of infected hepatopancreatocytes. These nucleocapsids comprise a missing link in the published literature on the replication cycle of MBV by providing evidence for the means by which the viral genome travels from the plasma membrane of the hepatopancreatocyte to the nucleus. Features similar to those of MBV from other areas, but not previously reported for MBV from Australia include empty capsids attached to the nuclear pore, central filaments in developing capsids, capsids partly filled with nucleic acid, and filaments in subapical envelope expansions. A model for virogenesis and replication is illustrated which takes into account the new observations as well as previously described ultrastructural characteristics of the developing viral particle.

Animals↗

PubMed2000

Search for a fourth-generation quark more massive than the Z0 boson in p&pmacr; collisions at radicals = 1.8 TeV

We present the results of a search for pair production of a fourth-generation charge -1 / 3 quark (b(')) in sqrt[s] = 1.8 TeV p&pmacr; collisions using 88 pb(-1) of data obtained with the Collider Detector at Fermilab. We assume that both quarks decay via the flavor-changing neutral current process b(')-->bZ(0) and that the b(') mass is greater than m(Z)+m(b). We studied the decay mode b(')b(');-->Z(0)Z(0)b&bmacr; where one Z0 decays into e(+)e(-) or &mgr;(+)&mgr;(-) and the other decays hadronically, giving a signature of two leptons plus jets. An upper limit on the sigma(p&pmacr;-->b(')b(');)x[B(b(')-->bZ(0))](2) is established as a function of the b(') mass. We exclude at 95% confidence level a b(') quark with mass between 100 and 199 GeV/c(2) for B(b(')-->bZ(0)) = 100%.

Journal Article↗

PubMed2000

Transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region from p&pmacr; collisions at sqrt

The transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region of 66<M(ee)<116 GeV/c(2) from p&pmacr; collisions at sqrt[s] = 1.8 TeV are measured using 110 pb(-1) of collisions taken by the Collider Detector at Fermilab during 1992-1995. The total cross section is measured to be 248+/-11 pb. The differential transverse momentum cross section is compared with calculations that match quantum chromodynamics perturbation theory at high transverse momentum with the gluon resummation formalism at low transverse momentum.

Journal Article↗

PubMed2000

Measurement of the helicity of W bosons in top quark decays

We use the transverse momentum spectrum of leptons in the decay chain t-->bW with W-->lnu to measure the helicity of the W bosons in the top quark rest frame. Our measurement uses a t&tmacr; sample isolated in 106+/-4 pb(-1) of data collected in p&pmacr; collisions at sqrt[s] = 1.8 TeV with the CDF detector at the Fermilab Tevatron. Assuming a standard V-A weak decay, we find that the fraction of W's with zero helicity in the top rest frame is F0 = 0.91+/-0. 37(stat)+/-0.13(syst), consistent with the standard model prediction of F0 = 0.70 for a top mass of 175 GeV/c(2).

Journal Article↗

PubMed2000

Observation of diffractive b-quark production at the fermilab tevatron

We report a measurement of the fraction of b quarks produced diffractively in &pmacr;p collisions at sqrt[s] = 1.8 TeV. Diffraction is identified by the absence of particles in a forward pseudorapidity region. From events with an electron of transverse momentum 9.5<p(e)(T)<20 GeV/ c within the pseudorapidity region |eta|<1.1, the ratio of diffractive to total b-quark production rates is found to be R(&bmacr;b) = [0.62+/-0.19(stat)+/-0.16(syst)]%. This result is comparable in magnitude to corresponding ratios for W and dijet production but significantly lower than expectations based on factorization.

Journal Article↗

PubMed2000

Anti-mesothelial markers in sarcomatoid mesothelioma and other spindle cell neoplasms.

AIMS: To undertake a comparative evaluation of three antimesothelial markers (thrombomodulin, cytokeratin 5/6 and calretinin) with broad spectrum cytokeratin (AE1/AE3) in differentiating between sarcomatoid mesothelioma and a spectrum of spindle cell neoplasms. METHODS AND RESULTS: Thirty-one malignant sarcomatoid mesotheliomas were studied. Calretinin expression was focally identified in 12 (39%) tumours and thrombomodulin and cytokeratin 5/6 immunoreactivity was seen in nine (29%) cases. In comparison there was strong diffuse cytoplasmic reactivity with the broad spectrum cytokeratin (AE1/AE3) in 24 of 31 (77%) tumours. Thirty mixed spindle cells neoplasms were studied. No calretinin expression was identified in any case. Thrombomodulin immunoreactivity was identified in four (16%) cases (two angiosarcomas, two high-grade sarcomas, not otherwise specified). Cytokeratin 5/6 expression was seen in one high-grade pulmonary sarcoma originally termed malignant fibrous histiocytoma. None of the antimesothelial markers was expressed in the four spindle cell carcinomas studied. In contrast, broad spectrum cytokeratin was diffusely expressed in all four spindle cell carcinomas (three pulmonary, one renal), both synovial sarcomas, both malignant mixed Müllerian tumours, one of three pulmonary leiomyosarcomas and two of nine sarcomas, not otherwise specified. CONCLUSIONS: Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.

Biomarkers, Tumor↗