Historical biogeography and diversification of ringless Amanita (section Vaginatae) support an African origin and suggest niche conservatism in the Americas.

Ectomycorrhizal fungi (ECM) sustain nutrient recycling in most terrestrial ecosystems, yet we know little about what major biogeographical events gave rise to present-day diversity and distribution patterns. Given the strict relationship between some ECM lineages and their hosts, geographically well-sampled phylogenies are central to understanding major evolutionary processes of fungal biodiversity patterns. Here, we focus on Amanita sect. Vaginatae to address global diversity and distribution patterns. Ancestral-state-reconstruction based on a 4-gene timetree with over 200 species supports an African origin between the late Paleocene and the early Eocene (ca. 56 Ma). Major biogeographic "out-of-Africa" events include multiple dispersal events to Southeast Asia (ca. 45-21 Ma), Madagascar (ca. 18 Ma), and the current Amazonian basin (ca. 45-36 Ma), the last two likely trans-oceanic. Later events originating in Southeast Asia involve Nearctic dispersal to North America (ca. 20-5 Ma), Oceania (Australia and New Zealand; ca. 15 Ma), and Europe (ca. 10-5 Ma). Subsequent dispersals were also inferred from Southeast Asia to East Asia (ca. 4 Ma); from North America to East Asia (ca. 11-8 Ma), Southeast Asia (ca. 19-2 Ma), Northern Andes (ca. 15 Ma), and Europe (ca. 15-2 Ma), respectively; and from the Amazon to the Caribbean region (ca. 25-20 Ma). Finally, we detected a significant increase in the net diversification rates in the branch leading to most northern temperate species in addition to higher state-dependent diversification rates in temperate lineages, consistent with previous findings. These results suggest that species of sect. Vaginatae likely have higher dispersal ability and higher adaptability to new environments, in particular compared to those of its sister clade, sect. Caesareae. Overall, the much wider distribution of A. sect. Vaginatae, from pan-tropical to pan-arctic, provides a unique window to understanding niche conservatism across a species-rich clade of ECM fungi.

Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR).

BACKGROUND: The 'treat to target' paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis. OBJECTIVES: To identify treatment targets in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). METHODS: Data from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate-severe, severe) and PASI (range 0-72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA. RESULTS: Data from 13 422 patients were available (58% male, 91% white ethnicity, mean age 44·9 years), including over 23 000 longitudinal PASI and PGA scores. An absolute PASI ≤ 2 was concordant with PASI 90 and an absolute PASI ≤ 4 was concordant with PASI 75 in 90% and 88% of cases, respectively. These findings were robust to subgroups of timing of assessment, baseline disease severity and treatment modality. PASI and PGA were strongly correlated (Spearman's rank correlation coefficient 0·92). The median PASI increased from 0 (interquartile range 0-0, range 0-23) to 19 (interquartile range 15-25, range 0-64) for PGA clear to severe, respectively. PGA clear/almost clear was concordant with PASI ≤ 2 in 90% of cases, and PGA moderate-severe severe was concordant with the National Institute for Health and Care Excellence PASI eligibility criteria for biologics in 81% of cases. CONCLUSIONS: An absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis. What's already known about this topic? The most commonly used relative disease activity measure in psoriasis is ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90); however, it has several limitations including dependency on a baseline severity assessment. Defining an absolute target disease activity end point in psoriasis has the potential to improve patient outcomes and reduce costs, as demonstrated by treat-to-target approaches in other chronic diseases such as hypertension and diabetes. The Physician's Global Assessment (PGA) is a popular alternative measure of psoriasis severity in daily practice; however, its utility has not been formally assessed with respect to PASI. What does this study add? An absolute PASI ≤ 2 corresponds with PASI 90 response and is a relevant disease end point for treat-to-target approaches in psoriasis. There is a strong correlation between PASI and PGA. PGA moderate-severe/severe may serve as an alternative eligibility criterion for biologics to PASI-based definitions, and PGA clear/almost clear is an appropriate alternative absolute treatment end point. What are the clinical implications of this work? Absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat-to-target management strategies in psoriasis.

Infliximab is associated with an increased risk of serious infection in patients with psoriasis in the U.K. and Republic of Ireland: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

BACKGROUND: Patients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections. OBJECTIVES: To compare the risk of serious infections associated with infliximab in patients with chronic plaque psoriasis against a cohort on nonbiologic systemic therapies. METHODS: A prospective cohort study was performed using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Infliximab was compared with nonbiologic systemic therapies, inclusive of any exposure to methotrexate, ciclosporin, acitretin, fumaric acid esters, psoralen-ultraviolet A or hydroxycarbamide. Serious infections were those associated with hospitalization, the use of intravenous antimicrobial therapy and/or those that led to death. Propensity score inverse probability treatment weights were used to adjust for potential confounding from a priori identified covariates. Cox proportional hazards models were calculated to obtain hazard ratios (HRs). RESULTS: In total, 3843 participants were included for analysis up to October 2016. The incidence rates were significantly higher in the infliximab cohort (47·8 per 1000 person-years) [95% confidence interval (CI) 35·7-64·0], compared with 14·2 per 1000 person-years (95% CI 11·5-17·4) in the nonbiologic systemic cohort. Infliximab was associated with an overall increase in the risk of serious infection compared with nonbiologics [adjusted HR (adjHR) 1·95, 95% CI 1·01-3·75] and methotrexate only (adjHR 2·96, 95% CI 1·58-5·57) and a higher risk of serious infection in the first 6 months of therapy (adjHR 3·49, 95% CI 1·14-10·70). CONCLUSIONS: Infliximab is associated with an increased risk of serious infections compared with nonbiologic systemic therapies in patients with psoriasis in the U.K. and the Republic of Ireland.

Toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

BACKGROUND: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. METHODS: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. RESULTS: In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms ("isoniazid arm" with moxifloxacin substituted for ethambutol & "ethambutol arm" with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91-1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55-7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59-6.10, p < 0.001). CONCLUSIONS: Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.

Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

BACKGROUND: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. OBJECTIVES: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). METHODS: The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. RESULTS: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. CONCLUSIONS: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.

Measurement of proton tunneling in short hydrogen bonds in single crystals of 3,5 pyridinedicarboxylic acid using nuclear magnetic resonance spectroscopy.

In this Letter, we present NMR spin-lattice and relaxometry data for proton transfer in one of the shortest known N-H⋯O hydrogen bonds in a single crystal of 3,5 pyridinedicarboxylic acid (35PDCA). It is widely believed that proton transfer by quantum tunneling does not occur in short hydrogen bonds since the ground state energy level lies above the potential barrier, yet these data show a temperature independent, proton tunneling rate below 77 K and a clear deviation from classical dynamics below 91 K. This study therefore suggests that proton tunneling occurs in all hydrogen bonds at low temperature and the crossover temperature to classical hopping must be determined when evaluating whether proton tunneling persists at higher temperature, for example in enzyme catalysis under physiological conditions.

[Morphological changes in the lumbar dorsal root ganglion of the domestic porcine after pulsed radiofrequency stimulation].

Pulsed radiofrequency (PRF) is a percutaneous minimal invasive procedure that can be used when conservative pain therapy methods have been ineffective. The effectiveness of PRF was demonstrated in various good quality randomized control studies, but mechanisms of action are still unclear. The aim of our study is to analyse the histological effects of PRF on the domestic porcine dorsal root ganglion (DRG), and evaluate the expression of biomarkers in gangliocytes. 3 domestic porcines were investigated. Under general anaesthesia and X-ray control, DRG PRF was performed. Four lumbar DRGs (L1, L2, L3, L4) were randomly treated. The opposite side DRGs was used as control. One month after the procedure the animal was euthanized. The lumbar region of the spine was placed in 10% formaldehyde for a month. After this fixation DRG samples were prepared for slide analysis. They were embedded in paraffin in order to obtain 3 microm thick sections, which were then cut by microtome and collected on slide glasses. Using standard immunohistochemical reactions, the materials were tinted to define biomarkers NF, GFAP, Hsp-70 expression and apoptosis by TUNEL kit. The number of cells with NF (26.0 +/- 3.0 vs 16.1 +/- 3.3; p < 0.05), GFAP (12.0 +/- 1.3 vs 3.2 +/- 0.9; p < 0.05) and Hsp-70 (10.0 +/- 1.6 vs 4.2 +/- 1.0; p < 0.05) expression, were larger in the PRF side comparing with the control side. Additionally, glial cells in spinal ganglia of both sides demonstrated immunoreactivity. The instances of apoptosis were not significantly different, in statistical terms, between the control and experimental sides (18.0 +/- 4.0 vs 20.0 +/- 4.0; p = 0.35). PRF in spinal gangliocytes of lumbar region increases neural tissue cytoskeleton factors like NF and GFAP suggesting about active regeneration processes into the cells 1 month after the procedure. Spinal gangliocytes one month after PRF treatment notably increases Hsp-70 expression suggesting about activation of cellular activity and inhibitory role reducing of oxidative stress. Similar number of apoptotic cells in spinal ganglia of lumbar region after PRF and control side suggests about inhibitory role of PRF on programmed cell death and stimulation of cell survival.

Regulation of hindbrain Pyy expression by acute food deprivation, prolonged caloric restriction, and weight loss surgery in mice.

PYY is a gut-derived putative satiety signal released in response to nutrient ingestion and is implicated in the regulation of energy homeostasis. Pyy-expressing neurons have been identified in the hindbrain of river lamprey, rodents, and primates. Despite this high evolutionary conservation, little is known about central PYY neurons. Using in situ hybridization, PYY-Cre;ROSA-EYFP mice, and immunohistochemistry, we identified PYY cell bodies in the gigantocellular reticular nucleus region of the hindbrain. PYY projections were present in the dorsal vagal complex and hypoglossal nucleus. In the hindbrain, Pyy mRNA was present at E9.5, and expression peaked at P2 and then decreased significantly by 70% at adulthood. We found that, in contrast to the circulation, PYY-(1-36) is the predominant isoform in mouse brainstem extracts in the ad libitum-fed state. However, following a 24-h fast, the relative amounts of PYY-(1-36) and PYY-(3-36) isoforms were similar. Interestingly, central Pyy expression showed nutritional regulation and decreased significantly by acute starvation, prolonged caloric restriction, and bariatric surgery (enterogastroanastomosis). Central Pyy expression correlated with body weight loss and circulating leptin and PYY concentrations. Central regulation of energy metabolism is not limited to the hypothalamus but also includes the midbrain and the brainstem. Our findings suggest a role for hindbrain PYY in the regulation of energy homeostasis and provide a starting point for further research on gigantocellular reticular nucleus PYY neurons, which will increase our understanding of the brain stem pathways in the integrated control of appetite and energy metabolism.

Morphology, Multilocus Phylogeny, and Toxin Analysis Reveal Amanita albolimbata, the First Lethal Amanita Species From Benin, West Africa.

Many species of Amanita sect. Phalloideae (Fr.) Quél. cause death of people after consumption around the world. Amanita albolimbata, a new species of A. sect. Phalloideae from Benin, is described here. The taxon represents the first lethal species of A. sect. Phalloideae known from Benin. Morphology and molecular phylogenetic analyses based on five genes (ITS, nrLSU, rpb2, tef1-α, and ß-tubulin) revealed that A. albolimbata is a distinct species. The species is characterized by its smooth, white pileus sometimes covered by a patchy volval remnant, a bulbous stipe with a white limbate volva, broadly ellipsoid to ellipsoid, amyloid basidiospores, and abundant inflated cells in the volva. Screening for the most notorious toxins by liquid chromatography-high-resolution mass spectrometry revealed the presence of α-amanitin, ß-amanitin, and phallacidin in A. albolimbata.

Mapping mycological ignorance - checklists and diversity patterns of fungi known for West Africa.

Scientific information about biodiversity distribution is indispensable for nature conservation and sustainable management of natural resources. For several groups of animals and plants, such data are available, but for fungi, especially in tropical regions like West Africa, they are mostly missing. Here, information for West African countries about species diversity of fungi and fungus-like organisms (other organisms traditionally studied by mycologists) is compiled from literature and analysed in its historical context for the first time. More than 16,000 records of fungi representing 4843 species and infraspecific taxa were found in 860 publications relating to West Africa. Records from the Global Biodiversity Information Facility (GBIF) database (2395 species), and that of the former International Mycological Institute fungal reference collection (IMI) (2526 species) were also considered. The compilation based on literature is more comprehensive than the GBIF and IMI data, although they include 914 and 679 species names, respectively, which are not present in the checklist based on literature. According to data available in literature, knowledge on fungal richness ranges from 19 species (Guinea Bissau) to 1595 (Sierra Leone). In estimating existing species diversity, richness estimators and the Hawksworth 6:1 fungus to plant species ratio were used. Based on the Hawksworth ratio, known fungal diversity in West Africa represents 11.4% of the expected diversity. For six West African countries, however, known fungal species diversity is less than 2%. Incomplete knowledge of fungal diversity is also evident by species accumulation curves not reaching saturation, by 45.3% of the fungal species in the checklist being cited only once for West Africa, and by 66.5% of the fungal species in the checklist reported only for a single country. The documentation of different systematic groups of fungi is very heterogeneous because historically investigations have been sporadic. Recent opportunistic sampling activities in Benin showed that it is not difficult to find specimens representing new country records. Investigation of fungi in West Africa started just over two centuries ago and it is still in an early pioneer phase. To promote proper exploration, the present checklist is provided as a tool to facilitate fungal identification in this region and to aid conceptualisation and justification of future research projects. Documentation of fungal diversity is urgently needed because natural habitats are being lost on a large scale through altered land use and climate change.

Critical influences affecting response to various treatments in young children with ADHD: a case series.

BACKGROUND: While the use of stimulant medication as a treatment for children with attention deficit hyperactivity disorder (ADHD) has been the most studied therapy in child psychiatry, there is debate about its use with young children. This study describes a series of cases seen in a normal clinical context, treated with one of four different treatment programmes. METHODS: Sixteen pre-school children diagnosed with ADHD and their parents were randomly assigned to receive one of four treatments: (1) 0.3 mg/kg methylphenidate, parent training programme; (2) 0.3 mg/kg methylphenidate, parent support programme; (3) placebo medication, parent training; and (4) placebo medication, parent support. Changes were assessed at the individual level, using clinical observations, parent and teacher rating scales and measures of parenting and family factors. RESULTS: Children were more likely to improve when the treatment involved at least one active component (medication or parent training). However, there was notable variability in individual parental and child participants' responses to all treatment conditions, indicating the importance of interactions between treatment variables and other factors. CONCLUSIONS: Findings are discussed within the framework of a transactional model, and inferences are drawn about the limitations of the idea that there is a 'best treatment' that is universally applicable.

Inkjet printable-photoactive all inorganic perovskite films with long effective photocarrier lifetimes.

Photoactive perovskite quantum dot films, deposited via an inkjet printer, have been characterized by x-ray diffraction and x-ray photoelectron spectroscopy. The crystal structure and bonding environment are consistent with CsPbBr3 perovskite quantum dots. The current-voltage (I-V) and capacitance-voltage (C-V) transport measurements indicate that the photo-carrier drift lifetime can exceed 1 ms for some printed perovskite films. This far exceeds the dark drift carrier lifetime, which is below 50 ns. The printed films show a photocarrier density 109 greater than the dark carrier density, making these printed films ideal candidates for application in photodetectors. The successful printing of photoactive-perovskite quantum dot films of CsPbBr3, indicates that the rapid prototyping of various perovskite inks and multilayers is realizable.

A high efficiency technique for the generation of transgenic sugar beets from stomatal guard cells.

An optimized protocol has been developed for the efficient and rapid genetic modification of sugar beet (Beta vulgaris L.). A polyethylene glycol-mediated DNA transformation technique could be applied to protoplast populations enriched specifically for a single totipotent cell type derived from stomatal guard cells, to achieve high transformation frequencies. Bialaphos resistance, conferred by the pat gene, produced a highly efficient selection system. The majority of plants were obtained within 8 to 9 weeks and were appropriate for plant breeding purposes. All were resistant to glufosinate-ammonium-based herbicides. Detailed genomic characterization has verified transgene integration, and progeny analysis showed Mendelian inheritance.

Location and orientation of lone pairs in apatite-type materials: a computational study.

Electron localisation function (ELF) calculations have been used to provide the first computational location of the cation lone pairs in apatite materials. We show that the orientation of the lone pairs varies depending on the identity and positions of the channel anions. The results represent a new platform for interpreting experimentally observed structure-property relationships in functional apatites. In particular, they have significant implications for ionic conductivity and suggest that structure-property relationships in lone-pair containing apatite-type solid electrolytes are more complex than previously thought.

Synthesis and characterisation of new Bi(iii)-containing apatite-type oxide ion conductors: the influence of lone pairs.

Lone-pair cations are known to enhance oxide ion conductivity in fluorite- and Aurivillius-type materials. Among the apatite-type phases, the opposite trend is found for the more widely studied silicate oxide ion conductors, which exhibit a dramatic decrease in conductivity on Bi(iii) incorporation. In this work, the influence of lone-pair cations on the properties of apatite-type germanate oxide ion conductors has been investigated by preparing and characterising seven related compositions with varying Bi(iii) content, by X-ray and neutron powder diffraction and impedance spectroscopy. All materials are very good oxide ion conductors (with conductivities of up to 1.29 × 10-2 S cm-1 at 775 °C). Increasing Bi(iii) content leads to increases in conductivity by up to an order of magnitude, suggesting significant differences in the oxide-ion conduction mechanisms between lone-pair-containing apatite-type germanate and silicate solid electrolytes.

Phenylthioalkylamines in experimental tumor treatment in mice.

Two phenylthioalkylamines, phenylthioethylamine (PTEA) and phenylthiopropylamine (PTPA), were prepared and tested for cytotoxicity in vitro and as antitumor agents in (C57BL X DBA/2)F1 (BDF1) mice. Low concentrations of PTEA (median effective concentrations of 8.0, 12.0, and 1.3 micrograms PTEA/ml) inhibited the growth of P388 murine lymphoma, L1210 leukemia, and B16 melanoma cells in culture. PTPA was more effective; concentrations of 0.80, 0.56, and 0.35 micrograms PTPA/ml inhibited the growth of P388, L1210, and B16 in vitro by 50%. PTEA and PTPA treatment increased survival times in BDF1 mice bearing the P388 lymphoma, L1210 leukemia, B16 melanoma, and Lewis lung tumors. Multiple daily administrations of the test compounds were more effective than single daily injections in increasing the life-span in mice bearing the P388 lymphoma and B16 melanoma. Both PTEA and PTPA inhibited the enzyme copper-zinc superoxide dismutase.

Correlation of serum, tumor, and liver serum glycoprotein: N-acetylneuraminic acid transferase activity with growth of the R3230AC mammary tumor in rats and relationship of the serum activity to tumor burden.

The observation that the activity of sialyltransferase (EC 2.4.99.1; serum glycoprotein:N-acetylneuraminic acid transferase) is often elevated in the serum of cancer patients necessitates an elucidation of the interrelationships of this serum enzyme with host tissues. Accordingly, the activity of this enzyme in serum, tumor, and liver was determined at various times after implantation of the R3230AC mammary carcinoma into Fischer rats. Results from samples obtained at numerous, sequential time points demonstrated that significant elevations in serum sialyltransferase enzyme activity occurred only in animals bearing large tumor burdens, i.e., greater than 20 g, or in animals with tumors present for longer than 21 days. In these tumor-bearing rats, the activity of sialyltransferase increased in liver tissue at 21 to 25 days concurrently with the increase in serum enzyme activity, suggesting that the liver may be a potential source of the serum enzyme. Sialyltransferase activity in tumor tissue was quite variable; the activity increased one week after tumor implantation and remained at the same level thereafter. When tumors were excised, the activity of the serum enzyme returned to control values within four days after surgery, suggesting that the half-life of serum sialyltransferase was two days. Serum enzyme levels were again elevated upon regrowth of the tumor. These results show that the serum sialyltransferase alters its activity in conjunction with changes in tumor burden.

Increased birth weights of National Wilms' Tumor Study patients suggest a growth factor excess.

An analysis of over 1800 patients with Wilms' tumor revealed significantly higher birth weights than newborns in the general United States population. The highest birth weights were found not only in patients diagnosed with the Beckwith-Wiedemann syndrome (mean, 3.78 kg), as had been expected, but also in those with hemihypertrophy (3.80 kg) or perilobar nephrogenic rests (3.56 kg) in addition to their Wilms' tumor. The birth weights of Wilms' tumor patients with intralobar nephrogenic rests (3.43 on average kg) and of those without associated anomalies (3.45 kg) were slightly but still significantly higher on average than national birthweights (overall mean, 3.35 kg) adjusted for gender, race, and year of birth in each subgroup. Birth weights of children with aniridia and Wilms' tumor (2.99 kg) were lower than the national mean. Among more than 3000 patients with Wilms' tumor, heights and weights at diagnosis were significantly higher for the subgroups of patients with Beckwith-Wiedemann syndrome or hemihypertrophy, and height was lower for those with aniridia or characteristic genitourinary anomalies, when compared to other patients with Wilms' tumor. These data suggest prenatal effects of growth factors on the development of Wilms' tumors, or vice versa, and provide further epidemiological support for heterogeneity in the pathogenesis of Wilms' tumors associated with perilobar nephrogenic rests versus intralobar nephrogenic rests.

The fractionation of suspensions of isolated hepatocytes by rate zonal centrifugation.

Parenchymal cells, isolated from rat liver by a simple non-enzymic technique, were fractioned according to ploidy class by rate zonal centrifugation on sucrose density gradients. This method of fractionation applied to liver cells prelabelled in vivo with tritiated thymidine separated different size classes of cells synthesising DNA.

Synthesis of complementary DNAs to partially purified mRNAs coding for the storage proteins of Pisum sativum (L).

mRNAs in developing cotyledons of Pisum sativum (L) coding for the major storage proteins, vicilin and legumin, were partially purified and characterized. Both vicilin (47 000 and 50 000 daltons) and legumin (60 000) precursor subunits were translated in the reticulocyte lysate cell-free system when driven by 18 S poly(A)+-RNA. Total poly(A)+-RNA, purified twice by oligo(dT)-cellulose chromatography, migrated on dissociating gels on electrophoresis as a polydisperse peak with three maxima at 18, 14 and 12 S. This mRNA preparation was used as a template for the synthesis of single- and double-stranded cDNAs under optimized reaction conditions. Analysis of single-stranded cDNA on dissociating gels showed a polydisperse profile, with three major components of molecular weights 3.7 x 10(5), 2.3 X 10(5) and 2.0 X 10(5). The double-stranded cDNA preparation contained some contaminating single strands, some partially double-stranded molecules formed by continuation of looped first strands, and some molecules which were primarily single strands protected by partial second strands. Restriction endonucleases cut the double-stranded cDNA preparation into several discrete fragments.