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Finchite (IMA2017-052), Sr(UO2)2(V2O8)·5H2O, is the first uranium mineral known to contain essential Sr. The new mineral occurs as yellow-green blades up to ~10 µm in length in surface outcrops of the calcrete-type uranium deposit at Sulfur Springs Draw, Martin County, Texas, U.S.A. Crystals of finchite were subsequently discovered underground in the Pandora mine, La Sal, San Juan County, Utah, U.S.A., as diamond-shaped golden-yellow crystals reaching up to 1 mm. The crystal structure of finchite from both localities was determined using single-crystal X-ray diffraction and is orthorhombic, Pcan, with a = 10.363(6) Å, b = 8.498(5) Å, c = 16.250(9) Å, V = 1431.0(13) Å3, Z = 4 (R1 = 0.0555) from Sulfur Springs Draw; and a = 10.3898(16), b = 8.5326(14), c = 16.3765(3) Å, V = 1451.8(4) Å3, Z = 4 (R1 = 0.0600) from the Pandora mine. Electron-probe microanalysis provided the empirical formula (Sr0.88K0.17Ca0.10Mg0.07Al0.03Fe0.02)Σ1.20(UO2)2(V2.08O8)·5H2O for crystals from Sulfur Springs Draw, and (Sr0.50Ca0.28Ba0.22K0.05)Σ0.94(U0.99O2)2(V2.01O8)·5H2O for crystals from the Pandora mine, based on 17 O atoms per formula unit. The structure of finchite contains uranyl vanadate sheets based upon the francevillite topology. Finchite is a possible immobilization species for both uranium and the dangerous radionuclide 90Sr because of the relative insolubility of uranyl vanadate minerals in water.

The Southern High Plains (SHP) is a new and emerging U.S. uranium province. Here, uranyl vanadates form deposits in Pliocene to Pleistocene sandstone, dolomite, and limestone. Fifteen calcrete uranium occurrences are identified; two of these, the Buzzard Draw and Sulfur Springs Draw deposits, have combined in-place resources estimated at about 4 million pounds of U3O8. Ore minerals carnotite and finchite are hosted in dolomite at the Sulfur Springs Draw deposit, with accessory fluorite, celestine, smectite/illite, autunite, and strontium carbonate. Host carbonate at the Sulfur Springs Draw deposit is ∼190 ka and mineralization mobilized as recently as 3.8 ka. Ash collected near the deposit is 631 ka and erupted from the Yellowstone caldera complex. The Triassic Dockum Group that contains sandstone-hosted uranium deposits throughout the region and underlies the SHP is a potential source for uranium and vanadium. Regional uplift and dissection reintroduced oxygenated groundwater into the Dockum Group, mobilizing uranium. Additional uranium may have been contributed to groundwater by weathering of volcanic ash in Pliocene and Pleistocene host rocks. The locations of the uranium occurrences are mostly in modern drainage systems in the southeast portion of the SHP. Modelling of modern groundwater in the SHP carried out in a parallel study shows that a single fluid could form carnotite through evaporation, and that fluids of the requisite composition are more prevalent in the southern portion of the SHP. The southeastern portion of the SHP hosts more uranium occurrences due to a variety of factors including (1) upward transport of groundwater and connectivity between source and host rock, (2) higher uranium and vanadium content of groundwater, (3) higher rates of groundwater recharge in this region to drive the mineralizing system, and (4) shallower groundwater facilitating surface evaporation. Ongoing erosion of host rocks challenges preservation of deposits and may limit their size.

At a former uranium pilot mill in Grand Junction, Colorado, mine tailings and some subpile sediments were excavated to various depths to meet surface radiological standards, but residual solid-phase uranium below these excavation depths still occurs at concentrations above background. The combination of fission-track radiography and scanning electron microscope energy-dispersive X-ray spectroscopy (SEM-EDS) provides a uniquely efficient and quantitative way of determining mineralogic associations of uranium that can influence uranium mobility. After the creation of sample thin sections, a mica sheet is placed on those thin sections and irradiated in a nuclear research reactor. Decay of the irradiated uranium creates fission tracks that can be viewed with a microscope. The fission-track radiography images indicate thin section sample areas with elevated uranium that are focus areas for SEM-EDS work. EDS spectra provide quantitative elemental data that indicate the mineralogy of individual grains or grain coatings associated with the fission-track identification of elevated uranium. For the site in this study, the results indicated that uranium occurred (1) with coatings of aluminum–silicon (Al/Si) gel and gypsum, (2) dispersed in the unsaturated zone associated with evaporite-type salts, and (3) sorbed onto organic carbon. The Al/Si gel likely formed when low-pH waters were precipitated during calcite buffering, which in turn retained or precipitated trace amounts of Fe, As, U, V, Ca, and S. Understanding these mechanisms can help guide future laboratory and field-scale efforts in determining long-term uranium release rates to groundwater.

High-U hydrothermal apatite with complex U Pb systematics is closely spatially associated with mineralization at the Coles Hill deposit, the largest unmined uranium deposit known in the United States. The deposit is hosted in metasomatized rocks of the 450- to 430-Ma-old Martinsville Intrusive Complex in south-central Virginia. Direct dating of metamict uranium-ore minerals, mostly coffinite, is not possible due to open-system radon loss. Instead, U Pb isotopes in cogenetic apatite were investigated as a means of evaluating the age of mineralization. Here we report in situ electron probe microanalyses (EPMA) of coffinite, isotope-dilution thermal-ionization mass spectrometry (ID-TIMS) U Pb data for mineralized whole rock samples, and laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) U Pb isotope data for apatite in both unmineralized and U-mineralized host rocks. Massive deficits in radiogenic Pb preclude reliable U Pb “chemical ages” calculated from EPMA data obtained from coffinite. In contrast, LA-ICPMS data for secondary apatite in unmineralized rocks indicate low-U concentrations (100–102 ppm), “normal” (consistent with models of terrestrial Pb isotopic evolution) initial Pb isotope compositions, and U Pb age estimates of ~330 Ma, which is consistent with dates previously proposed for the regional Paleozoic shear zone that hosts the deposit. Ore-stage apatite associated with coffinite has high-U concentrations (typically 102–103 ppm but up to 2.4 wt% U) and large excesses of 206Pb (207Pb/206Pb Pb dating of hydrothermal apatite. Excess 206Pb in apatite is derived from decay products of 222Rn lost from coffinite and mobilized by Na-, P-, and U-enriched metasomatic fluids during the main mineralizing event at ~230 Ma. Ore-stage alteration did not uniformly reset the U Pb systematics in host rocks precluding a well-constrained whole-rock isochron age. However, whole-rock isotope data imply U mobility at ~200–220 Ma and support a Triassic age for the final stages of mineralization. Results also indicate that apatite with up to several weight percent uranium is able to retain U and its decay products for hundreds of millions of years; an important consideration when assessing this mineral as a potential matrix for long-term storage of radioactive waste.

The coincidence of a number of geologic and climatic factors combined to create conditions favorable for the development of mineable concentrations of uranium hosted by Eocene through Pliocene sandstones in the Texas Coastal Plain. Here 254 uranium occurrences, including 169 deposits, 73 prospects, 6 showings and 4 anomalies, have been identified. About 80 million pounds of U3O8 have been produced and about 60 million pounds of identified producible U3O8 remain in place. The development of economic roll-type uranium deposits requires a source, large-scale transport of uranium in groundwater, and deposition in reducing zones within a sedimentary sequence. The weight of the evidence supports a source from thick sequences of volcanic ash and volcaniclastic sediment derived mostly from the Trans-Pecos volcanic field and Sierra Madre Occidental that lie west of the region. The thickest accumulations of source material were deposited and preserved south and west of the San Marcos arch in the Catahoula Formation. By the early Oligocene, a formerly uniformly subtropical climate along the Gulf Coast transitioned to a zoned climate in which the southwestern portion of Texas Coastal Plain was dry, and the eastern portion humid. The more arid climate in the southwestern area supported weathering of volcanic ash source rocks during pedogenesis and early diagenesis, concentration of uranium in groundwater and movement through host sediments. During the middle Tertiary Era, abundant clastic sediments were deposited in thick sequences by bed-load dominated fluvial systems in long-lived channel complexes that provided transmissive conduits favoring transport of uranium-rich groundwater. Groundwater transported uranium through permeable sandstones that were hydrologically connected with source rocks, commonly across formation boundaries driven by isostatic loading and eustatic sea level changes. Uranium roll fronts formed as a result of the interaction of uranium-rich groundwater with either (1) organic-rich debris adjacent to large long-lived fluvial channels and barrier–bar sequences or (2) extrinsic reductants entrained in formation water or discrete gas that migrated into host units via faults and along the flanks of salt domes and shale diapirs. The southwestern portion of the region, the Rio Grande embayment, contains all the necessary factors required for roll-type uranium deposits. However, the eastern portion of the region, the Houston embayment, is challenged by a humid environment and a lack of source rock and transmissive units, which may combine to preclude the deposition of economic deposits. A grade and tonnage model for the Texas Coastal Plain shows that the Texas deposits represent a lower tonnage subset of roll-type deposits that occur around the world, and required aggregation of production centers into deposits based on geologic interpretation for the purpose of conducting a quantitative mineral resource assessment.

This paper is divided into two sections, both concerned with the effects of chronic denervation on Schwann cells. The first group of experiments explore the proposal that lengthy denervation produces changes in Schwann cells in vivo that compromise axonal regeneration. The second group of experiments compare the molecular phenotypes of acutely and chronically denervated Schwann cells in vitro, and examine their responses to an exogenously applied neuregulin.

Prostacyclins are extensively used to treat pulmonary arterial hypertension (PAH), a life-threatening disease involving the progressive thickening of small pulmonary arteries. Although these agents are considered to act therapeutically via the prostanoid IP receptor, treprostinil is the only prostacyclin mimetic that potently binds to the prostanoid EP2 receptor, the role of which is unknown in PAH. We hypothesised that EP2 receptors contribute to the anti-proliferative effects of treprostinil in human pulmonary arterial smooth muscle cells (PASMCs), contrasting with selexipag, a non-prostanoid selective IP agonist. Human PASMCs from PAH patients were used to assess prostanoid receptor expression, cell proliferation, and cyclic adenosine monophosphate (cAMP) levels following the addition of agonists, antagonists or EP2 receptor small interfering RNAs (siRNAs). Immunohistochemical staining was performed in lung sections from control and PAH patients. We demonstrate using selective IP (RO1138452) and EP2 (PF-04418948) antagonists that the anti-proliferative actions of treprostinil depend largely on EP2 receptors rather than IP receptors, unlike MRE-269 (selexipag-active metabolite). Likewise, EP2 receptor knockdown selectively reduced the functional responses to treprostinil but not MRE-269. Furthermore, EP2 receptor levels were enhanced in human PASMCs and in lung sections from PAH patients compared to controls. Thus, EP2 receptors represent a novel therapeutic target for treprostinil, highlighting key pharmacological differences between prostacyclin mimetics used in PAH.

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging.

The bone morphogenetic protein (BMP) type II receptor (BMPR-II) is predominantly expressed on the vascular endothelium in the adult lung. Although mutations in BMPR-II are known to underlie many cases of familial pulmonary arterial hypertension (FPAH), little is known regarding the expression of BMPs and their signalling pathways during normal lung development or the impact of BMPR-II mutations on endothelial cell function. We determined the cellular localization and expression levels of BMP4, BMP receptors, and activation of downstream signalling via phospho-Smad1 in a developmental series of human embryonic and fetal lungs by immunohistochemistry. The expression of BMP4 and BMP receptors was temporally and spatially regulated during lung development. BMPR-II expression correlated with phosphorylation of tissue Smad1 and was highest during the late pseudoglandular and early canalicular stage of lung development, when vasculogenesis is intense. Phospho-Smad1 expression was associated with markers of proliferation in endothelial cells. In vitro studies confirmed that BMPs 2 and 4 induced phosphorylation of Smad1/5 and pulmonary artery endothelial cell (PAEC) migration and proliferation. Adenoviral transfection of PAECs with mutant kinase-deficient BMPR-II, or siRNA knockdown of BMPR-II, inhibited Smad signalling and the proliferative response to BMP4. Our findings support a critical role for BMPs in lung vasculogenesis. Dysfunctional BMP signalling in PAECs during development may lead to abnormal pulmonary vascular development and contribute to the pathogenesis of FPAH.

Many studies have shown a role of retinoid signalling in neurite outgrowth in vitro, and that the retinoic acid receptor (RAR) beta2 is critical for this process. We show here that RARbeta2 is expressed predominantly in dorsal root ganglia (DRG) neuronal subtypes that express neurofilament (NF) 200 and calcitonin gene-related peptide (CGRP), and that these neurons extend neurites in response to RA. We demonstrate that retinoid signalling has a role in neurite outgrowth in vivo, by showing that in a peripheral nerve crush model there is less neurite outgrowth from RARbeta null DRG compared to wild-type. We identify sonic hedgehog (Shh) as a downstream target of the RARbeta2 signalling pathway as it is expressed in the injured DRG of wild-type but not RARbeta null mice. This regulation is direct as when RARbeta2 is overexpressed in adult motoneurons Shh is induced in them. Finally we show that Shh alone cannot induce neurite outgrowth but potentiates RARbeta2 signalling in this process.

Between August 1972 and March 1981, ten patients with metastatic breast cancer presented to M.D. Anderson Hospital and Tumor Institute at Houston Medical Breast Clinic with cranial nerve palsies (incidence, 0.13%). Eight of ten patients had extensive metastases at the base of the skull that was causing cranial nerve compression. Two patients had no bone involvement and were suspected to have soft tissue disease, one retro-orbitally and the other at the base of the skull. None of the patients had evidence of intracranial disease. The most frequently affected cranial nerves were V and VII, with 70% and 60% of patients having palsies of these nerves respectively. The estimated median survival of the patients from time of onset of cranial nerve palsy was 20 months; the palsies improved in 50% of patients who received regional therapy.

Immediately after birth the adluminal vascular SMCs of the pulmonary elastic arteries undergo transient actin cytoskeletal remodeling as well as cellular de-differentiation and proliferation. Vascular smooth muscle phenotype is regulated by serum response factor, which is itself regulated in part by the negative regulator YY1. We therefore studied the subcellular localization of YY1 in arteries of normal newborn piglets and piglets affected by neonatal pulmonary hypertension. We found that YY1 localization changed during development and that expression of γ-smooth muscle actin correlated with expression of cytoplasmic rather than nuclear YY1. Analysis of the regulation of YY1 localization in vitro demonstrated that polymerized γ-actin sequestered EGFP-YY1 in the cytoplasm and that YY1 activation of c-myc promoter activity was inhibited by LIM kinase, which increases actin polymerization. Consistent with these data siRNA-mediated down-regulation of YY1 in C2C12 cells increased SM22-α expression and inhibited cell proliferation. Thus, actin polymerization controls subcellular YY1 localization, which contributes to vascular SMC proliferation and differentiation in normal pulmonary artery development. In the absence of actin depolymerization, YY1 does not relocate to the nucleus, and this lack of relocation may contribute to the pathobiology of pulmonary hypertension.

This is a proof of principle report showing that fibres of Bioglass® 45S5 can form a biocompatible scaffold to guide regrowing peripheral axons in vivo. We demonstrate that cultured rat Schwann cells and fibroblasts grow on Bioglass® fibres in vitro using SEM and immunohistochemistry, and provide qualitative and quantitative evidence of axonal regeneration through a Silastic conduit filled with Bioglass® fibres in vivo (across a 0.5 cm interstump gap in the sciatic nerves of adult rats). Axonal regrowth at 4 weeks is indistinguishable from that which occurs across an autograft. Bioglass® fibres are not only biocompatible and bioresorbable, which are absolute requirements of successful devices, but are also amenable to bioengineering, and therefore have the potential for use in the most challenging clinical cases, where there are long inter-stump gaps to be bridged.

We have previously described the production of large cables of fibronectin, a large extracellular matrix cell adhesion glycoprotein, which has a potential application in tissue engineering. Here we have stabilised these cables for longer survival and looked at their ultrastructural cell–substrate behaviour in vitro. Dissolution experiments showed that low concentrations of copper not only caused significant material stabilisation but left pores which could promote cell ingrowth, as we have previously reported with Fn-mats. Indeed, the greatest amount of cell ingrowth was observed for copper treated cables. Immunostaining showed S-100 + multi-layers of cells around the edge of cables while ultrastructural analysis confirmed the presence of a mixture of fibroblasts and bipolar cells associated with fragments of basal lamina, which is a Schwann cell phenotype. Interestingly, the outermost layers of cells consisted of S-100 − cells, presumed fibroblasts, apparently ‘capping’ the Schwann cells. Toxicity tests revealed that Schwann cells were only able to grow at the lowest concentration of copper used (1 μ m ) while fibroblasts grew at all concentrations tested. These results could be used to design biomaterials with optimum properties for promoting cellular ingrowth and survival in tissue engineered grafts which may be used to improve peripheral nerve repair.

Expression of the normal cellular form of prion protein is both necessary and rate-limiting in the spread of prion disease, yet its cellular expression in vivo is poorly understood. To optimise immunohistochemical labelling of this protein in mouse brain, we have developed novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue. Expression was found to be predominantly neuronal, and to differ between different classes of neurone. Thus, neurones immunoreactive for GABA expressed very high levels of normal prion protein; most projection neurones expressed much lower levels, particularly on their axons in the major fibre tracts, and some neurones (e.g. those positive for dopamine) displayed no detectable prion protein. In marked contrast, all neurones, even those that were immunonegative, expressed high levels of message for prion protein, shown by non-radioactive in situ hybridisation. Glia expressed very low levels of message, and undetectable levels of prion protein. We conclude that the steady-state level of prion protein, which differs so markedly between different neuronal types, is primarily controlled post-transcriptionally, possibly by differences in protein trafficking or degradation. These marked differences in the way different neurones produce and/or degrade their normal cellular prion protein may influence the selective spread and neurotoxic targeting of prion diseases within the CNS.

Recent studies on human embryonic and fetal lungs show that the pulmonary arteries form by vasculogenesis. Little is known of the early development of the pulmonary veins. Using immunohistochemical techniques and serial reconstruction, we studied 18 fetal and neonatal lungs. Sections were stained with antibodies specific for endothelium (CD31, von Willebrand factor) and smooth muscle (alpha and gamma smooth muscle actin, smooth muscle myosin, calponin, caldesmon, and desmin) and antibodies specific for the matrix glycoprotein tenascin, the receptor protein tyrosine kinase EphB4, and its ligand ephrinB2. Kiel University-raised antibody number 67 (Ki67) expression allowed qualitative assessment of cell replication. By 34 d gestation, there was continuity between the aortic sac, pulmonary arteries, capillaries, pulmonary veins, and atrium. The pulmonary veins formed by vasculogenesis in the mesenchyme surrounding the terminal buds during the pseudoglandular period and probably by angiogenesis in the canalicular and alveolar stages. EphB4 and ephrinB2 did not distinguish between presumptive venous and arterial endothelium as they do in mouse. All venous smooth muscle cells derived directly from the mesenchyme, gradually acquiring smooth muscle specific proteins from 56 d gestation. Thus, both pulmonary arteries and veins arise by vasculogenesis, but the origins of their smooth muscle cells and their cytoskeletal protein content are different.

Peripheral pulmonary arteries remodel immediately after birth as pulmonary vascular resistance falls. We hypothesised that there is a link between the response to agonist stimulation and wall structure in early postnatal life. Arteries from fetal, newborn and 14-day-old piglets were mounted on a perfusion myograph. Lumen diameter and smooth muscle cell nuclear positions were recorded after sequential addition of KCl, U46619 and bradykinin. Subsequently, vessels were studied by confocal and transmission electron microscopy. Contractile agonist stimulation caused a greater and faster reduction in lumen diameter in the newborn than at 14 days (p < 0.02) and the distance between cells decreased more in the newborn (p < 0.05). Unstimulated smooth muscle cells changed shape from being rounded in the fetus to fusiform by 14 days, with increasing length/width ratio (p < 0.01). On contraction, length/width ratio decreased most at 14 days (p < 0.01). Extracellular matrix, collagen and elastin, sparse at birth, increased by 14 days. Thus a greater change in lumen diameter in relation to cellular contraction was observed in the newborn than at 14 days and the amount of extracellular matrix within the vessel wall may affect the overall change in lumen diameter.

Axonal degeneration is a major cause of permanent deficit in inflammatory neurological diseases such as multiple sclerosis. Axons undergo degeneration specifically at the site of the inflammatory lesions, suggesting that locally produced inflammatory factors mediate the phenomenon. One such factor is nitric oxide (NO), which we have previously reported can cause reversible conduction block in axons. Here we confirm these observations and extend them to show that axons exhibit the early stages of wallerian degeneration if they are conducting impulses at physiological frequencies while they are exposed to the low micromolar concentrations of NO that are likely to occur at sites of inflammation. Rat dorsal roots were concurrently exposed in vivo to both NO and sustained impulse activity at 1, 50, or 100 Hz. Although our in vivo observations necessarily focused on the more acute responses, morphological examination of exposed roots at the end of the recording period revealed nodal and paranodal changes consistent with acute wallerian degeneration in roots stimulated at 50 or 100 Hz. This interpretation was confirmed in a few experiments that were prolonged to permit more obvious indicators of degeneration to develop. In these experiments the formation of myelin ovoids and frank axonolysis occurred in more than 95% of fibers. Roots stimulated at only 1 Hz appeared normal. We propose that the combination of normal impulse traffic and NO at sites of inflammation may cause axonal degeneration and that electrical activity may therefore be an important factor in causing permanent disability in patients with neuroinflammatory disorders.

Recent studies on the morphogenesis of the pulmonary arteries have focused on nonhuman species such as the chick and the mouse. Using immunohistochemical techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular matrix proteins. Cell replication was also assessed. Serial reconstruction showed a continuity of circulation between the heart and the capillary plexus from at least 38 d of gestation. The intrapulmonary arteries appeared to be derived from a continuous expansion of the primary capillary plexus that is from within the mesenchyme, by vasculogenesis. The arteries formed by continuous coalescence of endothelial tubes alongside the newly formed airway. Findings were consistent with the pulmonary arterial smooth muscle cells being derived from three sites in a temporally distinct sequence: the earliest from the bronchial smooth muscle, later from the mesenchyme surrounding the arteries, and last from the endothelial cells. Despite their different origins, all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age. The order of appearance of these maturing proteins was from the subendothelial cells outward across the vessel wall and from hilum to periphery. The airways would seem to act as a template for pulmonary artery development. This study provides a framework for studying the signaling mechanisms controlling the various aspects of lung development.

Objective: Neural crest-derived cells were previously shown to participate in vessel wall formation of the great thoracic arteries, and their contribution was proposed to affect morphology and physiology of these vessels in the chick. The present investigation was undertaken to examine vascular differentiation and morphogenesis of the neural crest-derived aortic arches in mammals. Methods: Using immunohistochemical markers for smooth muscle cell differentiation and a neurofilament marker, we examined morphogenesis of the great arteries in mice, ranging from embryonic day 11.5 to the adult. Results: We observed that in the 4th aortic arch arteries early media formation differed from the other arteries, in that they almost completely lacked (or showed decreased) actin expression in certain areas. This discontinuity in actin expression persisted throughout much of foetal development, in the form of circular segments of cells displaying decreased staining for smooth muscle markers, both at the left and right side of the arterial tree. In adult mice, the 4th arch artery derivatives, segment B of the aortic arch and the proximal right subclavian artery, were observed to differ from adjoining vessels in their smooth muscle and elastic composition. Staining for neurofilaments revealed close association of the developing segments with apparent sensory afferent vascular innervation. Conclusion: The unique areas of the 4th arch artery identified here reflect the basic segmental patterning of the early embryonic pharyngeal arches. These segments correlate with sites that are predisposed to interruption or severe hypoplasia, and may thus reveal part of the aetiology of type-B aortic arch interruptions and arteria lusoria.

We describe the macroscopic and microscopic anatomy of the posterior interosseous (PIN) and median nerves, at the arcade of Frohse and pronator arch respectively, in nerves obtained from five cadavers. Nerves were either constricted at sites of potential entrapment; appeared swollen proximal to these sites; or exhibited neither swelling nor constriction. Renaut bodies were present in all nerves. In the PIN, most Renaut bodies were found beneath a tendinous arcade of Frohse, whereas in the median nerve most were found proximal to the pronator arch. We propose that since Renaut bodies appear to displace normal endoneurial components, and may be associated with low-grade axonal drop-out, their presence may adversely affect the functional outcome of surgical decompression of either the PIN or median nerve.

Aim: to examine women's attempts at control during labour in water. Design: an exploratory design consisting of tape-recorded, in-depth interviews using the grounded theory approach. Setting: a medium sized town in the south of England. The data were collected in the maternity unit of a local general hospital set in a semi-rural location. Participants: nine women who had chosen to spend their labour process in water. The participants selected had experienced a normal pregnancy and given birth to a healthy baby at term. Findings: labour in water was seen by all but one of the participants as beneficial, particularly as they felt that this gave them more control over the process. They valued their own involvement in determining the outcome of their care. The support of the midwife in making decisions was seen as necessary to remain in control. Conclusions: labour in water was a positive experience for this group of healthy women. The feeling of freedom to make decisions, however, was balanced with a wish for the support of the midwife.

The authors describe two patients who required massive doses of benzodiazepines to treat complicated alcohol and sedative withdrawal delirium. Some of the factors that contribute to difficulties in management are discussed. Finally, we describe the advantages and disadvantages of high dose pharmacologic management and controversies regarding psychopharmacologic management of such complex patients.

In October 1992 the World Health Organization (WHO) set up a health monitoring programme in the former Yugoslavia to obtain information on communicable disease upon which to base decisions about medical aid requirements. This paper covers the first year of the programme (October 1992–October 1993) and details the steps taken to set it up. Information was sought from personal contacts, ‘ad hoc’ sources (United Nations agencies and non-governmental organizations) and the health authorities of the regions of former Yugoslavia. An attempt was made to establish a sentinel monitoring system to provide routine data to allow health predictions to be made. A bulletin was produced to disseminate surveillance results and health advice. The system obtained sufficient data (mostly from ‘ad hoc’ sources) for WHO to take informed decisions about medical aid but the sentinel system was not established successfully.

Carbonates from the ~1100–1450 Ma old Proterozoic Belt Supergroup were collected from stratigraphic sections throughout Montana and Idaho, USA. The sampled sequences, in ascending stratigraphic order, include the Newland, Altyn, Spokane/Greyson transition, Empire, Wallace, Helena, Siyeh, Snowslip, Shepard, and Libby formations. An increase in the degree of postdepositional alteration of Belt limestones is reflected in a diminution of Sr and Mg contents, an increase in Mn, and depletion in 13C and 18O. Two diagenetic trends can be resolved for the limestones. One, affecting the presumed originally aragonite-rich sediments, includes carbonates from the Lower Belt Newland Formation. In contrast, the Middle Belt Carbonate (Wallace, Helena, Siyeh formations) may have been originally of high-Mg calcitic mineralogy. Projection of the alteration trends for the Lower and Middle Belt limestones suggest ~21‰ SMOW and ~ +2.5‰ to +1.0‰ PDB as the best preserved values for the δ18O and δ13C of seawater, respectively; both comparable to results from other Mesoproterozoic carbonate sequences. The oxygen isotope data for limestones show a regional westward depletion of ~8‰ in 18O, possibly reflecting a higher temperature of postdepositional alteration in the western Belt basin. This depletion in 18O is accompanied by a comparable decrease in δ13C values, most likely because a higher proportion of carbon was incorporated from CO2 generated by thermal cracking of hydrocarbons at depth. Dolostones in the Belt basin are dominantly micritic, with good preservation of depositional textures. Chemically and isotopically, their alteration trends mimic those of limestones, leading to comparable projected “best” values for δ13C. 87Sr/86Sr values of Belt carbonates range between 0.70484 and 0.74991. Progressive diagenesis, as indexed by decreasing concentrations of Sr and depletions in 18O and 13C, results in an increase in 87Sr/ 86Sr values. The least radiogenic measurement, from a Lower Belt Newland limestone sample, appears to fit reasonably well into the general trend for Proterozoic seawater, as discussed in Mirota and Veizer (1994). This and the consistency of δ18O and δ13C in limestones with other coeval sequences suggests that the (Lower and Middle) Belt carbonate sections are marine, deposited in an environment that was not continuously separated from the open ocean.

A relapsing and remitting axonal polyneuropathy developed in a woman at age 47. Serial electrophysiological studies showed that the amplitudes of compound muscle action potentials and sensory action potentials were reduced but conduction velocities were only mildly slowed. F wave latencies were normal and there was no evidence of conduction block. Two sural nerve biopsy specimens showed changes supportive of axonal neuropathy. Repeated responses to prednisolone alone and later prednisolone and azathioprine suggested that inflammatory, possibly autoimmune, processes were important in this case of chronic relapsing axonal neuropathy.

The objective of this study was to describe trends in neonatal meningitis in England and Wales during the years 1975-91. Laboratory reports and, for the years 1983-91, data on statutory notifications and deaths from neonatal meningitis were reviewed. The mean annual total of laboratory reports of neonatal bacterial meningitis 1975-91 was 109 cases (range 69-133) with a slight upward trend apparent in the latter half of the study period. The mean annual number of reports of neonatal viral meningitis was only 14 cases with no trend apparent. The leading bacteria isolated were group B streptococci, Escherichia coli, and Listeria monocytogenes accounting for 34.1%, 28.5%, and 6.8% of reports, respectively. There was a change in the pattern of causative bacteria from 1981 onwards with the group B streptococcus displacing E coli as the leading cause. With respect to neonatal viral meningitis, echoviruses and coxsackie viruses accounted for 55.4% and 38.6% of cases, respectively. Neonatal meningitis was seriously undernotified; the ratio of laboratory reported cases to cases notified ranged from 12:1 in 1985 to 4:1 in 1989. The annual numbers of deaths ranged from 18 to 39. The laboratory reporting system provided the most useful data on secular trends and causative organisms for neonatal meningitis. The slight upward trend in the number of reports of bacterial meningitis merits continued surveillance.

Endothelin receptor antagonists are used to treat idiopathic pulmonary arterial hypertension (IPAH), but human pulmonary arterial endothelin receptor expression is not well defined. We hypothesised that disease and treatment would modify normal receptor distribution in pulmonary resistance arteries of children. Using immunohistochemistry and semiquantitative analysis, we investigated endothelin receptor subtypes A and B (ET(A) and ET(B), respectively), and endothelial nitric oxide synthase (eNOS) expression in peripheral pulmonary arteries of tissue from untreated children with IPAH (n=7), following extended combined bosentan and epoprostenol therapy (n=5) and from normal subjects (n=5). Clinical, haemodynamic and pathological abnormalities were severe and advanced in all IPAH cases. ET(A) was detected in pulmonary arterial endothelial cells of all normal and diseased tissue and cultured cells. Endothelial ET(A), ET(B) and eNOS expression was reduced in patent, plexiform and dilatation lesions of untreated cases, but in treated cases, ET(A) and ET(B) were normal and eNOS increased. In smooth muscle, ET(A) expression was reduced in treated cases but ET(B) expression increased in all arteries of both treated and untreated cases. In summary, ET(A) is expressed on human pulmonary arterial endothelium. In IPAH, combination treatment with bosentan and epoprostenol had a more marked influence on endothelin receptor expression of endothelial than smooth muscle cells.

The diagnosis of congenital infection is unlikely to form a significant part of most paediatric practice outside the neonatal period. Nevertheless, the list of organisms which can cross the placenta is growing and for many the long term effects await elucidation. It has been recommended that the term ‘TORCH’ syndrome or testing be abandoned’ because it does not encompass all the relevant organisms (including two of the three discussed in this review) or encourage focused diagnosis. Instead, the physician should decide on the basis of clinical features in individual patients which diagnosis is most likely and take appropriate specimens for identification of specific infections. This approach will be illustrated below by describing the diagnosis of congenitally acquired toxoplasmosis, parvovirus B 19 and listeriosis. These three infections have also been selected for review because each is an ‘old’ disease with a ‘new’ issue for the 1990s (Table 1). One other issue is that of the steadily increasing HIV epidemic among women, which has specific implications for each infection addressed individually below.

Radial/concentric and twinned/sparry ooids from the upper Belt Supergroup originally formed as mixed Mgcalcite and aragonite, and aragonite. Textural evidence suggests that Mgcalcite ooids may have formed along with the ooids having an original aragonite mineralogy. Strontium concentrations of 2400 to 2900 ppm support an aragonitic precursor to the twinned/sparry ooids, and Sr values of 2500 ppm strongly suggest that the radial/concentric ooids had an aragonitic component in addition to the Mgcalcite suggested by the preserved fabric. Trace element (Mn, Mg, Fe, and Sr) values of ooids and early carbonate cements suggest that diagenetic trends for these Proterozoic carbonates are similar to those established for their Phanerozoic and Archean counterparts. Mg, Fe, and Mn increase and Sr decreases with successively later carbonate phases.

Prostacyclin analogs, used to treat idiopathic pulmonary arterial hypertension (IPAH), are assumed to work through prostacyclin (IP) receptors linked to cyclic AMP (cAMP) generation, although the potential to signal through peroxisome proliferator-activated receptor-γ (PPARγ) exists.IP receptor and PPARγ expression may be depressed in IPAH. We wished to determine if pathways remain functional and if analogs continue to inhibit smooth muscle proliferation.We used Western blotting to determine IP receptor expression in peripheral pulmonary arterial smooth muscle cells (PASMCs) from normal and IPAH lungs and immunohistochemistry to evaluate IP receptor and PPARγ expression in distal arteries.Cell proliferation and cAMP assays assessed analog responses in human and mouse PASMCs and HEK-293 cells. Proliferative rates of IPAH cells were greater than normal human PASMCs. IP receptor protein levels were lower in PASMCs from patients with IPAH, but treprostinil reduced replication and treprostinil-induced cAMP elevation appeared normal. Responses to prostacyclin analogs were largely dependent on the IP receptor and cAMP in normal PASMCs, although in IP(-/-) receptor cells analogs inhibited growth in a cAMP-independent, PPARγ-dependent manner. In IPAH cells, antiproliferative responses to analogs were insensitive to IP receptor or adenylyl cyclase antagonists but were potentiated by a PPARγ agonist and inhibited (∼ 60%) by the PPARγ antagonist GW9662. This coincided with increased PPARγ expression in the medial layer of acinar arteries.The antiproliferative effects of prostacyclin analogs are preserved in IPAH despite IP receptor down-regulation and abnormal coupling. PPARγ may represent a previously unrecognized pathway by which these agents inhibit smooth muscle proliferation.

We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain-Barre syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally identified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain-Barre syndrome.

The expression and function of the 8 distinct catalytic isoforms of PI 3-kinase (PI3K) in the nervous system are unknown. Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110delta isoform has previously been shown to be enriched in leukocytes. Here we report that p110delta is also highly expressed in the nervous system. Inactivation of p110delta in mice did not affect gross neuronal development but led to an increased vulnerability of dorsal root ganglia neurons to exhibit growth cone collapse and decreases in axonal extension. Loss of p110delta activity also dampened axonal regeneration following peripheral nerve injury in adult mice and impaired functional recovery of locomotion. p110delta inactivation resulted in reduced neuronal signaling through the Akt protein kinase, and increased activity of the small GTPase RhoA. Pharmacological inhibition of ROCK, a downstream effector of RhoA, restored axonal extension defects in neurons with inactive p110delta, suggesting a key role of RhoA in p110delta signaling in neurons. Our data identify p110delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system.

The aim of this study was to describe the anatomy of the extensor pollicis brevis tendon, in particular its insertion, in 44 preserved hands from 23 cadavers. We found that only 25% of the tendons were inserted in the conventional way, viz, into the base of the proximal phalanx, and confirmed that the course and insertion of the extensor pollicis brevis tendon varies widely. The importance of these findings to the practice of hand surgery is discussed.