Lacustrine radiations in African Synodontis catfish.

Synodontis catfish are a species-rich, tropical pan-African genus that predominately occur in fluviatile environments, but which also form a small radiation within Lake Tanganyika (LT). Here we estimate Synodontis relationships, based on mitochondrial and nuclear DNA, greatly expanding previous sampling. Data were analysed using different methods of phylogenetic inference: Bayesian (also testing compositional heterogeneity), likelihood and parsimony, in order to investigate biogeographic history and the extent of intralacustrine speciation within this group. Bayesian-relaxed clock analyses were used to estimate timings of radiations. Our analyses reveal a single origin of the LT flock with the inclusion of the nonendemic S. victoriae, and that these taxa evolved relatively recently (5.5 Ma), considerably later than the formation of LT (9-12 Ma). Two internal endemic clades diversified at a similar time (2-2.5 Ma), corresponding to a period of climate change, when lake levels dropped. We find evidence for a further species flock, composed of riverine southern African taxa, the diversification of which is very rapid, 0.8 Ma (95% HPD: 0.4-1.5) and infer a similar scenario for the diversification of this flock to southern African serrachromine cichlids in that they radiated in the now extinct lake Makgadikgadi. We also reveal that the biogeographic history of Synodontis catfish is more complex than previously thought, with nonmonophyletic geographic species groupings.

Sleep stage and personality characteristics of "natural" long and short sleepers.

A group of college freshmen that typically slept 5(1/2) hours or less per night and a group that typically slept 9(1/2) hours or more did not differ significantly on a battery of personality, scholastic, and medical measures. Compared with control subjects not selected on a sleep length criterion, electroencephalograph recordings of the short sleepers contained reduced amounts of stage 2 and rapid eye movement sleep.

Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: preliminary screening for selection of potentially-responsive biomarkers.

BACKGROUND: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. METHODS: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-alpha had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. CONCLUSIONS: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.

Role of the stem cell factor (SCF) receptor and the alternative forms of its ligand (SCF) in the induction of long-term growth by stroma cells.

Self renewal and differentiation of hematopoietic stem cells is regulated by the hematopoietic microenvironment. The Stem Cell Factor (SCF) has been shown to be one of the essential factors that governs stem cell maintenance. In this abstract we describe a functional analysis of the membrane bound and soluble SCF within the context of stroma cocultures with hematopoietic cells. We report that transmembrane SCF is essential for long term growth, whereas soluble SCF supports only short term proliferation of stroma dependent hematopoietic cells. We also show that the SCF/c-kit interaction can be substituted by an unknown mechanism. To determine the molecular mechanism involved in maintenance of hematopoietic cells on stroma we analyzed the c-kit expression during coculture. We demonstrate that c-kit expression was downregulated during coculture. Downregulation was induced by the coculture itself and not by external factors.

The role of soluble growth factors in inducing transient growth and clonal extinction of stroma cell dependent erythroblastic leukemia cells.

A coculture system of a murine erythroblastic leukemia cell line (ELM-D) with its supportive stromal cell line (MS-5) was established. Long-term growth of ELM-D cells is strictly stroma cell dependent. Interaction between stem cell factor (SCF) and its receptor, c-kit, was demonstrated to be important for stroma cell-dependent growth by anti c-kit neutralizing monoclonal antibody (mAb) inhibition experiments. Significantly, soluble growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or SCF of MS-5 stromal cells (MS-5 CM) could replace the requirement of stroma cells for a considerable period. However, ELM-D cells maintained in these growth factors underwent clonal extinction after 3-6 weeks unless contact with stroma was re-established. Furthermore, IL-3 or GM-CSF acted in a dominant manner in inducing cell death in the presence of stroma cells. Cells showing clonal extinction undergo programmed cell death and do not differentiate. These altered growth properties of ELM-D cells exposed to soluble growth factors or to stroma cells appear to be analogous to those described for T or B cells primed by antigen presenting cells and then grown in growth factors.

PTH regulates fetal blood calcium and skeletal mineralization independently of PTHrP.

PTH and PTHrP both act in the regulation of fetal mineral metabolism. PTHrP regulates placental calcium transfer, fetal blood calcium, and differentiation of the cartilaginous growth plate into endochondral bone. PTH has been shown to influence fetal blood calcium, but its role in skeletal formation remains undefined. We compared skeletal morphology, mineralization characteristics, and gene expression in growth plates of fetal mice that lack parathyroids and PTH (Hoxa3 null) with the effects of loss of PTHrP (Pthrp null), loss of PTH/PTHrP receptor (Pthr1 null), and loss of both PTH and PTHrP (Hoxa3 null x Pthrp null). Loss of PTH alone does not affect morphology or gene expression in the skeletal growth plates, but skeletal mineralization and blood calcium are significantly reduced. In double-mutant fetuses (Hoxa3 null/Pthrp null), combined loss of PTH and PTHrP caused fetal growth restriction, limb shortening, greater reduction of fetal blood calcium, and reduced mineralization. These findings suggest that 1) PTH may play a more dominant role than PTHrP in regulating fetal blood calcium; 2) blood calcium and PTH levels are rate-limiting determinants of skeletal mineral accretion; and 3) lack of both PTH and PTHrP will cause fetal growth restriction.

The prokaryotic neomycin-resistance-encoding gene acts as a transcriptional silencer in eukaryotic cells.

The gene encoding neomycin resistance (neo) mediates a cis-acting negative effect on expression from promoters in transient and stable transfectants of mammalian cell lines. Inserting the neo gene either into retroviral vectors or into plasmids containing reporter genes results in a five- to tenfold decrease of expression from proximal promoters like the simian virus 40 early or the retroviral myeloproliferative sarcoma virus promoter. The silencing effect is not dependent on the insertion site or the orientation of the fragment. The neo gene is frequently used in eukaryotic vectors as a dominant selectable gene. Other selectable genes were tested for potential cis-activity. We found that the gene conferring resistance to puromycin from Streptomyces alboniger does not influence adjacent promoters.

The analysis of stable isotopes in urine to determine the fractional absorption of zinc.

We measured isotopic enrichment in urine after oral and intravenous administration of stable isotopes of zinc to determine fractional absorption (FA). 68Zn and 70Zn were administered orally and intravenously to four normal adults. Subsequently, urine and fecal samples were collected for 7 and 14 d, respectively, ashed, and passed through ion-exchange columns to separate zinc from other elements. Samples were analyzed by fast-atom-bombardment mass spectrometry. From 32 h onwards the enrichment of 68Zn and 70Zn in urine declined proportionately so that FA could be determined as follows: FA = enrichment (oral/iv) x dose (iv/oral). FA determinations from urine and feces (cumulative excretion) were, respectively, for subject ZK1, urine 0.79 +/- 0.03 and feces 0.70 +/- 0.01; ZK2, 0.79 +/- 0.05 and 0.69 +/- 0.02; ZK3, 0.26 +/- 0.01 and 0.25 +/- 0.01; and ZK4, 0.41 +/- 0.02 and 0.37 +/- 0.02. ZK1 and ZK2 received the oral isotope while fasting whereas ZK3 and ZK4 received the oral isotope with meals. FA of zinc can be determined by measurement of isotope enrichment in urine.

Zinc absorption in premature infants: comparison of two isotopic methods.

The fractional absorption of an oral dose of zinc can be measured in adults when given simultaneously with an intravenous dose and subsequently measuring the ratio of the double isotopic enrichment of urine. To test this method in very-low-birth-weight (VLBW) premature infants [n=5 females and 7 males, 1160 +/- 290 g (chi +/- SD) birth weight, 29 +/- 4 wk gestational age], an oral dose of either 300 or 1200 micrograms 68Zn.kg(-1).d(-1) was equilibrated with formula or human milk and administered simultaneously with either 50 or 100 micrograms 70Zn.kg(-1).d(-1) given intravenously 35 +/- 3 wk postconception. Urine and fecal samples were collected for 3-6 d and analyzed by inductively coupled plasma mass spectrometry. Endogenous fecal zinc (EFZ) was determined from isotopic enrichment, whereas net absorption and retention were calculated by traditional methods. The mean fractional absorption calculated from urine was 0.22 +/- 0.09 and from feces it was 0.25 +/- 0.07. Zinc intake averaged 1821 +/- 330, fecal excretion 1637 +/- 419, and urinary excretion 67 +/- 30 micrograms.kg(-1).d(-1). EFZ averaged 390 +/- 270 micrograms.kg(-1).d(-1) and ranged from 48 to 889 micrograms.kg(-1).d(-1). Net absorption was 220 +/- 316 micrograms.kg(-1).d(-1) and net retention was 131 +/- 334 micrograms.kg(-1).d(-1). True absorption was 373 +/- 161 micrograms.kg(-1).d(-1). Fecal collection is difficult, tedious, and often incomplete, and may be replaced by urine collection for the fractional absorption of zinc in groups of premature infants.

Nutritional patterns of mothers of children with neural tube defects in Newfoundland.

In an exploratory study of the genetic epidemiology of neural tube defects in Newfoundland, we studied mothers who had given birth to a child with a neural tube defect (NTD) with respect to their nutrition, as well as various other factors. The frequency of NTD in the area studied was 3.5/1,000 births and has not decreased recently, as it has in some other parts of the world. Twenty-five mothers of children with NTD and a comparison group (CG), matched for age and neighbourhood, completed 3 day dietary records. The NTD group consisted of all mothers who had given birth to an NTD child within the previous 3.5 years in the chosen area. The CG mothers were ascertained through the local public health nurse who chose the nearest unaffected child born in the same time period as the NTD probands. NTD mothers were younger, heavier, and of lower socioeconomic status than were CG mothers. CG group women consumed more vitamin supplements during the periconceptional period (P < 0.05) and consumed more dairy and cereal products, fruits and vegetables (other than potatoes), and fewer sweets than did NTD mothers. Sixty-four percent of NTD mothers had folacin intakes below the recommended level (168 mg) compared to 27% of CG mothers (P < 0.01). These findings support previous evidence that poor maternal nutrition, and low dietary folate in particular, increase the chance of having a child with an NTD, and emphasize the need for supplementary folate in the diet of women of childbearing age in areas where the frequency of NTDs is high.

Inhibition of p38 mitogen activated protein kinase increases lipopolysaccharide induced inhibition of apoptosis in neutrophils by activating extracellular signal-regulated kinase.

BACKGROUND: Prolonged polymorphonuclear neutrophil (PMN) survival has been implicated in tissue injury after sepsis. Previously we reported that lipopolysaccharide (LPS) inhibits PMN apoptosis via the activation of the extracellular signal-regulated kinase (ERK). Conversely, the p38 mitogen activated protein kinase (MAPK) pathway is involved in the spontaneous apoptosis of PMNs. The interaction between these 2 pathways and their ability to regulate apoptosis during sepsis remain largely undefined. We hypothesize that there is interaction between the ERK and p38 pathways during sepsis. METHODS: PMNs were isolated from healthy volunteers by Ficoll gradient centrifugation and red blood cell sedimentation. Cells were then pretreated for 1 hour with the ERK inhibitor (PD98059, 10 micromol/L), p38 inhibitor (SB203580, 1 micromol/L), or vehicle. After treatment with LPS, apoptosis and MAPK activity were correlated. RESULTS: LPS stimulation significantly inhibits PMN apoptosis compared with unstimulated cells. Furthermore, inhibition of ERK significantly abrogates this effect, whereas inhibition of p38 augments LPS induced inhibition of apoptosis. Elk-1 phosphorylation (ERK target) is significantly increased by LPS alone and by inhibition of the p38 pathway during LPS stimulation. This correlates with ERK phosphorylation by Western blot. CONCLUSIONS: These data show that p38 inhibition enhances ERK activity during endotoxemia. Furthermore, these data suggest that cooperation between ERK and p38 MAPK pathways dictates the apoptotic potential of PMNs during inflammatory states.

Saving the photons: mapping X-rays by position-tagged spectrometry.

Since the early years of X-ray spectrometry in electron microscopes, mapping the locations of chemical elements has been important. The X-rays needed in large numbers for this are rare, owing to poor production efficiency compared with electron signals, and at risk of loss by many mechanisms such as missing the limited solid angle of the detector, absorption before reaching the detector and pulse pile-up conventional digital mapping hardware reduces the information contained in the X-ray spectrum at each pixel to the itegrated counts from a few regions of interest.The acquisition technique of position-tagged spectrometry eliminates the conflict between the desire to see full frame X-ray images quickly versus the analytical advantages of having complete spectra for each pixel. As the beam is scanned rapidly relative to traditional X-ray mapping, photons are counted in a virtual 3-D multichannel analyser on disk, preserving both spatial and spectral information. Along with the sophisticated post-processing allowed by storing an entire spectrum per pixel, a unique degree of dynamic interaction with the developing data is made possible by integrating many short scans instead of using a single long dwell time at each pixel.

Zinc requirement of premature infants.

Premature infants require adequate amounts of zinc to foster growth and cognitive development. Zinc given during TPN (450-500 micrograms.kg-1.day-1) is the only way to meet in utero accretion rates before 36 wk postconceptional age because of extensive resecretion into the gut of oral zinc. After that time, infants should be consuming formulas supplemented with 12 mg/L zinc for the whole of infancy.

Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement.

To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.

Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition.

Thirty infants were randomly assigned to receive either 3 mL of MVI-Pediatric supplement (PAR3 group, parenterally fed) or 2 mL (PAR2 group, parenterally fed). For the first week, 100% received total parenteral nutrition (TPN), 50% by the second, and less than 33% by the third. Eighteen control infants received enteral feeds of infant formula. Baseline (before TPN) and subsequent weekly blood samples, dietary data, and 24-hour urine collections were obtained. The adequacies of thiamine and riboflavin were assessed by the thiamine pyrophosphate effect and erythrocyte glutathione reductase activity, respectively. Urinary thiamine and riboflavin levels were measured by fluorometry. Plasma folate, red blood cell folate, urinary folate, and plasma vitamin B12 concentrations were determined by radioassay. No differences between groups were observed in thiamine pyrophosphate effect, erythrocyte glutathione reductase activity, urinary B1 or B2, or red blood cell folate levels at any time. Plasma folate differed (p less than .05) among the PAR3 group (24 +/- 7 ng/mL), and both the PAR2 (13 +/- 5 ng/mL) and enterally fed (ENT) groups (16 +/- 3 ng/mL) before the initiation of feeds, at week 1 (PAR3 = 32 +/- 15 ng/mL; PAR2 = 18 +/- 4 ng/mL; ENT = 19 +/- 9, ng/mL) and between the PAR3 (30 +/- 16 ng/mL) and PAR2 (16 +/- 4 ng/mL) infants at week 2. Plasma vitamin B12 levels differed among the ENT groups (551 +/- 287 pg/mL) and both the parenteral groups (PAR2 = 841 +/- 405 pg/mL; PAR3 = 924 +/- 424 pg/mL) at week 1 and between the ENT (530 +/- 238 pg/mL) and PAR3 (999 +/- 425 pg/mL) groups at week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition.

BACKGROUND: Intravenous iron supplements are not routinely administered to very-low-birth-weight newborns receiving total parenteral nutrition because of the possible increased risk of infection and because iron needs may be met with blood transfusions. METHODS: To assess the benefits of a prudent IV iron supplement (200 to 250 micrograms/kg/d), 26 very-low-birth-weight newborns (birth weight, 1005 +/- 302 g; gestational age, 28 +/- 2.3 weeks; mean +/- SD) were randomly allocated to receive total parenteral nutrition without iron (No-Iron) or with iron supplied as iron dextran (Iron). These newborns were followed at baseline (2 to 3 days after birth) and at weeks 1 to 4 thereafter. At each sampling time, urine samples, fecal samples (rarely), unused total parenteral nutrition solutions, blood products, and a blood sample (1 mL) were collected. RESULTS: There were no differences between the two groups in anthropometric measurements, hematologic or biochemical parameters, number or amount of blood transfusions (2.3 +/- 1.9), amount of blood removed for diagnostic purposes (44 +/- 16 mL), or number of septic events (n = 16). There was no difference between the groups for the total iron excreted; however, the Iron group retained more iron. Iron balance was negative for all but 10 newborns (No-Iron, 3; Iron, 7) throughout the study. CONCLUSIONS: A total iron intake of 400 micrograms/kg/d, half of which was provided by IV iron, is not sufficient to maintain iron balance or to meet fetal accretion rates (1000 micrograms/kg/d) in very-low-birth-weight newborns receiving total parenteral nutrition. Furthermore, endogenous iron from blood transfusions does not provide an adequate supply of iron.

Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition.

BACKGROUND: Molybdenum (Mo) is an essential trace element required by three enzymatic systems, yet there are no reports of Mo deficiency in infants. Low-birth-weight infants (LBW) might be at risk for Mo deficiency because they are born before adequate stores for Mo can be acquired, they have rapid growth requiring increased intakes, and they frequently receive supplemental parenteral nutrition (SPN) and total parenteral nutrition (TPN) unsupplemented with molybdenum. METHODS: To investigate Mo requirements of LBW infants (n = 16; birth weight, 1336+/-351 g; gestational age, 29.8+/-2.5 weeks; M+/-SD), the authors collected all feeds, urine, and feces prior to TPN (baseline, n = 16, collections = 16), during TPN (n = 9, collections = 19), during SPN (n = 13, collections = 17), and after one week of full oral feeds (FOFs) of formula or human milk (FOF, n = 16, collections = 16). RESULTS: Infant weights at collection times were: 1.3+/-0.3 g, 1.27+/-0.4 g, 1.4+/-0.3 g, and 1.7+/-0.5 g, respectively. Mo intake was 0.03+/-0.1 microg/d, 0.34+/-0.1 microg/d, 1.25+/-1.7 microg/d, and 6.1+/-2.5 microg/d. Mo output was 0.64+/-0.6, 0.34+/-0.5, 0.68+/-0.8, and 4.1+/-2.5 microg/d. Mo balance at these times was -0.60+/-0.5, -0.001+/-0.5, 0.57+/-1.9, and 2.0+/-2.9 microg/d. Mo balance increased with time, yet some infants were always in negative balance, even though Mo intakes exceeded recommendations. CONCLUSIONS: The authors speculate that an intravenous intake of 1 microg/kg/d (10 nmol/kg/d) and an oral intake of 4-6 microg/kg/d (40-60 nmol/kg/d) would be adequate for the LBW infant.

Tertiary gain and disability syndromes.

Since the introduction of the concept of tertiary gain by Dansak in 1973, there has been little further publication or research on this topic. Yet, tertiary gain is often the subject of debate amongst physicians, therapists, insurers, the media, and even at times the general public. Much of the controversy of disability syndromes and the health and economic burden they present has focused on secondary gain and illness behaviour. The role of tertiary gain in illness behaviour is likely also relevant, and a model of tertiary gain is needed to begin further understanding the implications of this phenomenon for patients and those who treat them. This article introduces a phraseology for tertiary gain, and models the effects of tertiary gain on illness behaviour and the interactions of secondary and tertiary gain in the setting of disability syndromes.

Cognitive theory and illness behavior in disability syndromes.

There are many controversial disability syndromes, representing medicolegal and social dilemmas for a variety of medical disciplines. While illness behavior and sick role phenomena are often invoked to explain many of these syndromes, the extent to which such phenomena are under volitional control has not been thoroughly explored. The volitional control of illness behavior has important treatment implications, and may explain why cognitive therapy can be effective in these patients. Further understanding of the relevance of cognitive theory to illness behavior, the sick role, secondary gain, and disability may render even more effective cognitive therapy approaches. This review explores the consciousness states, the role of each state in information processing (in this case processing illness information), the automaticity and hence volitional state of each level of information processing, and the likelihood that illness behavior in disability syndromes is volitional. The cognitive model of these syndromes considers the interaction of automaticity, volition, and illness behavior and likely has numerous clinical, social, and legal applications.

Are syndromes in environmental medicine variants of somatoform disorders?

To date, relatively little is known about the etiology, pathophysiology, diagnosis, therapy, prevention and prognosis of environment-related syndromes like multiple chemical sensitivity (MCS), idiopathic environmental intolerance (IEI), sick building syndrome (SBS), chronic fatigue syndrome (CFS), candida syndrome (CS) and burnout syndrome (BS). Part of the reason is that these syndromes have not been clearly defined and classified in scientific categories distinct from each other, and that they show clinical similarities to classified somatoform disorders. Furthermore, there are at least three possible explanations for the existence of these syndromes: (1) The syndromes may result from the interaction of environmental factors, individual susceptibility and psychological factors (i.e., how they are perceived and seen by the patient); (2) they may reflect socially and culturally accepted methods of expressing distress; and/or (3) they may be iatrogenic. Despite all the uncertainties in evaluation of environmental syndromes, physicians have the duty to take the affected person's problems seriously. A comprehensive systematic classification which better accounts for these complex clinical manifestations is long overdue. Until these syndromes are well defined, the terms used for them should definitely not be applied to connote a specific disease process.