Recent developments in health insurance and life insurance case law.
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Employee Retirement Income Security Act↗
Biomedical subjects
J L Smith
Publications and source records attributed to J L Smith.
Raised levels of maternal serum secretory acetylcholinesterase may be indicative of fetal neural tube defects in early pregnancy.
BACKGROUND: To investigate the levels of maternal serum secretory acetylcholinesterase from a sample of pregnancies involving fetal neural tube defects and compare those results with alphafetoprotein levels. METHODS: Secretory acetylcholinesterase levels were measured using a new Enzyme Capture Immunoassay, in a small blind prospective study. The study group comprised pregnancies covering a gestational age range of 13-24 weeks where 98 had normal fetuses, 21 suffered from neural tube defects, and 15 had other complications. RESULTS: Maternal serum secretory acetylcholinesterase levels were found to be low and independent of gestational age between 14-20 weeks in a sample of normal pregnancies with normal alphafetoprotein levels. Raised levels of maternal serum secretory acetylcholinesterase were found in 100% of pregnancies involving spina bifida (17/17) and three of four anencephalics compared with raised alphafetoprotein levels found in 88% (15/17), and 100% (4/4) of the same samples. Only seven of 13 maternal serum samples from pregnancies with a normal outcome and none of the four twin pregnancies, all with raised alphafetoprotein levels, had raised secretory acetylcholinesterase levels. CONCLUSIONS: Raised levels of maternal serum secretory acetylcholinesterase may provide a useful indicator of neural tube defects in early pregnancy.
Acetylcholinesterase↗
Foveal cone dysfunction syndrome.
Our objective was to describe and expand the clinical spectrum of a rarely detected, previously reported photoreceptor disorder restricted to the foveal cones. Three patients with bilaterally decreased acuity and hemeralopia were examined to exclude a structural, vascular, inflammatory, or degenerative process. Each patient underwent a full neuroophthalmic examination, including full-field and focal cone electroretinogram (ERG). All three patients had normal-appearing fundi, mild dyschromatopsia, central or paracentral visual field depressions, normal full-field photopic and scotopic ERGs, and markedly reduced focal, foveal cone ERG responses. One patient had a ring scotoma and an asymptomatic family member with abnormal full-field and focal cone ERG. The syndrome of acquired foveal cone dysfunction presents as a bilateral, painless, progressive central visual loss with minimal or absent fundus changes. It eludes diagnosis until focal, foveal cone ERG is performed.
Aged↗
Correlations between cholesterol, vitamin E, and vitamin K1 in serum: paradoxical relationships to established epidemiological risk factors for cardiovascular disease.
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Adult↗
Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat.
Origins of hyperlipidemia and cholestasis that occur during pregnancy were investigated by examining expression of key elements related to plasma and hepatic cholesterol metabolism during pregnancy, lactation, and post-lactation in the rat model. Among major findings were: during pregnancy, the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl coenzyme A:cholesterol acyltransferase, acyl coenzyme A:diacylglycerol acyltransferase, cholesterol 7alpha-hydroxylase, cholesterol ester hydrolases, low density lipoprotein receptors, LRP, and mdr2 were significantly lower or similar to non-pregnant controls while SR-B1 was elevated. Once lactation began, reductase, cholesterol acyltransferase, 7alpha-hydroxylase activities, low density lipoprotein receptors, and mdr2 increased while SR-B1 decreased. In later stages of lactation most hepatic elements returned to near control levels. Plasma cholesterol levels were higher than control at birth and during lactation with increase in LDL-size particles. By 24 h post-lactation, plasma triglycerides were 3.7-fold higher while cholesterol remained unchanged. Very large lipoproteins were present while LDL-size particles were now absent. Hepatic cholesterol acyltransferase had decreased to 27% of control while diacylglycerol acyltransferase increased 3-fold and low density lipoprotein receptors doubled. Most elements were normalized 3 weeks after weaning except for LRP and low density lipoprotein receptors which were elevated. These studies provide an integrated picture of expression of key elements of hepatic and plasma cholesterol metabolism during pregnancy and lactation and advance understanding of hyperlipidemia and cholestasis during these states.
Animals↗
Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in normal fibroblasts treated with ethidium bromide and fibroblasts from a patient with mtDNA depletion syndrome.
Although much progress has been made in identifying genetic defects associated with mitochondrial diseases, the protein expression patterns of most disorders are poorly understood. Here we use immunochemical techniques to describe subunit expression patterns of respiratory chain enzyme complexes II (succinate dehydrogenase: SD) and IV (cytochrome c oxidase: COX) in cultured cells lacking mtDNA (Rho0 cells) derived either chemically by exposure of normal cells to ethidium bromide, or genetically in cells derived from a patient with mtDNA depletion syndrome. Both control cells and early passage patient-derived cells express a normal complement of SD and COX subunit proteins. Ethidium bromide treatment of normal cells and in vitro cell proliferation of patient-derived cells caused both populations to acquire identical Rho0 phenotypes. As expected, they lack mtDNA-encoded subunits COX-I and COX-II. In contrast, nDNA-encoded subunits are affected differentially, with some (COX-VIc) lacking and others (COX-IV, COX-Va, SD 30 and SD 70) maintained at somewhat reduced levels. We suggest that the differential stability of nDNA-encoded subunits in the absence of intact enzyme complexes is due to the ability of some, but not all, subunits to associate as partial complexes in the absence of mtDNA-encoded subunits.
Cells, Cultured↗
Use of gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo magnetic resonance angiography in the preoperative evaluation of living renal allograft donors.
BACKGROUND: Renal allograft retrieval from live donors requires an accurate determination of kidney anatomy including the renal arterial supply. Traditionally, conventional angiography has served as the gold standard for obtaining this information. More recently, magnetic resonance angiography (MRA) has been compared with conventional angiography. Although MRA has been shown to be more cost effective and to have none of the co-morbidity associated with the angiographic process, it still has been perceived to be less accurate than angiography. METHODS: We compared images obtained using a relatively new technique of gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo MRA with surgical findings in 15 living renal donors. In addition, average patient charge for MRA was compared with that of conventional angiogram. RESULTS: Fourteen patients were evaluated with the gadolinium-enhanced, ultrafast, three-dimensional, spoiled gradient-echo modality and the findings confirmed at surgery. On one occasion, a discrepancy occurred in which an accessory renal artery was suggested on the MRA but was not detected by conventional angiography. The accessory renal artery was later encountered at surgery. MRA was also used to evaluate patient 15 but was unsuccessful due to technical error. This patient was later found to have a positive cross-match with the recipient and therefore did not undergo surgery. CONCLUSIONS: We have found the gadolinium-enhanced MRA technique to be 100% accurate and as reliable as conventional angiography in determining renal vascular anatomy in living kidney donors. Additionally, it shares none of the associated potential angiographic complications and allows a 31% cost savings over angiography.
Contrast Media↗
Biological identity and diversity in photosynthesis and respiration: structure of the lumen-side domain of the chloroplast Rieske protein.
BACKGROUND: The cytochrome b6f complex functions in oxygenic photosynthesis as an integral membrane protein complex that mediates coupled electron transfer and proton translocation. The Rieske [2Fe-2S] protein subunit of the complex functions at the electropositive (p) membrane interface as the electron acceptor for plastoquinol and donor for the cytochrome f subunit, and may have a dynamic role in catalyzing electron and proton transfer at the membrane interface. There are significant structure/function similarities to the cytochrome bc1 complex of the respiratory chain. RESULTS: The 1.83 A crystal structure of a 139-residue C-terminal fragment of the Rieske [2Fe-2S] protein, derived from the cytochrome b6f complex of spinach chloroplasts, has been solved by multiwavelength anomalous diffraction. The structure of the fragment comprises two domains: a small 'cluster-binding' subdomain and a large subdomain. The [2Fe-2S] cluster-binding subdomains of the chloroplast and mitochondrial Rieske proteins are virtually identical, whereas the large subdomains are strikingly different despite a common folding topology. A structure-based sequence alignment of the b6f and bc1 groups of Rieske soluble domains is presented. CONCLUSIONS: The segregation of structural conservation and divergence in the cluster-binding and large subdomains of the Rieske protein correlates with the overall relatedness of the cytochrome b6f and bc1 complexes, in which redox domains in the aqueous p phase are dissimilar and those within the membrane are similar. Distinct sequences and surface charge distributions among Rieske large subdomains may provide a signature for interaction with the p-side oxidant protein and for the pH of the intraorganelle compartment.
Amino Acid Sequence↗
Phenotypic and functional characterization of mice that lack the type I receptor for IL-1.
IL-1 alpha and IL-1 beta bind to receptors termed the type I and type II IL-1 receptors. The type I IL-1 receptor is responsible for specific signaling, while the type II IL-1 receptor functions as a nonsignaling decoy receptor. To determine the effect of a defect in IL-1-mediated signaling, mice have been produced with a genetically disrupted type I IL-1 receptor gene. Mice lacking type I IL-1 receptors are of normal vigor and exhibit no overt phenotype. B cells from type I IL-1R-/- mice activated in vitro with anti-IgM do not proliferate in response to IL-1, but do so in response to IL-4. Injection of murine IL-1 alpha does not induce detectable serum IL-6 levels in type I IL-1R-/- mice, but equivalent levels are produced in response to LPS. Type I IL-1R-/- mice have normal serum Ig levels and generate equivalent primary and secondary Ab responses as wild-type mice. In response to LPS, acute phase protein mRNA induction are equivalent in type I IL-1R-/- and wild-type mice. Type I IL-1R-/- mice do not differ from control mice in susceptibility to either a lethal challenge with D-galactosamine plus LPS or high dose LPS. Interestingly, ICE-/-/type I IL-1R-/- double mutant mice are resistant to high dose LPS. Type I IL-1R-/- mice backcrossed to the C57BL/6 background were as equally resistant as wild-type mice to Listeria monocytogenes.
Acute-Phase Proteins↗
Coupled formation of an amidotransferase interdomain ammonia channel and a phosphoribosyltransferase active site.
Activation of gluatmine phosphoribosylpyrophosphate (RPPP) amidotransferase (GPATase) by binding of a PRPP substrate analog results in the formation of a 20 A channel connecting the active site for glutamine hydrolysis in one domain with the PRPP site in a second domain. This solvent-inaccessible channel permits transfer of the NH3 intermediate between the two active sites. Tunneling of NH3 may be a common mechanism for glutamine amidotransferase-catalyzed nitrogen transfer and for coordination of catalysis at two distinct active sites in complex enzymes. The 2.4 A crystal structure of the active conformer of GPATase also provides the first description of an intact active site for the phosphoribosyltransferase (PRTase) family of nucleotide synthesis and salvage enzymes. Chemical assistance to catalysis is provided primarily by the substrate and secondarily by the enzyme in the proposed structure-based mechanism. Different catalytic and inhibitory modes of divalent cation binding to the PRTase active site are revealed in the active conformer of the enzyme and in a feedback-inhibited GMP complex.
Amidophosphoribosyltransferase↗
Mechanism of the synergistic end-product regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase by nucleotides.
De novo purine nucleotide synthesis is regulated, at least in part, by end-product inhibition of glutamine PRPP amidotransferase. An important feature of this inhibition is the fact that certain synergistic nucleotide pairs give more than additive inhibition. The physiological importance of synergism is in amplifying regulation by the adenine and guanine nucleotide end products of de novo synthesis. Using a new method to quantitate synergism, ADP plus GMP were confirmed [Meyer, E., and Switzer, R. L. (1978) J. Biol. Chem. 254, 5397-5402] to give strong synergistic inhibition of Bacillus subtilis glutamine PRPP amidotransferase. An X-ray structure of the ternary enzyme.ADP.GMP complex established that ADP binds to the allosteric A site and GMP to the catalytic C site. GMP increased the binding affinity of ADP for the A site by approximately 20-fold. Synergism results from a specific nucleotide-nucleotide interaction that is dependent upon a nucleoside diphosphate in the A site and a nucleoside monophosphate in the C site. Furthermore, synergism is enhanced by the competition between nucleotide inhibitor and PRPP substrate for the C site. Purine base specificity results from a backbone carbonyl interaction of Lys305' with the 6-NH2 group of adenine in the A site and a Ser347 Ogamma interaction with the 2-NH2 group of guanine in the C site. Steric considerations favor binding of the nucleoside diphosphate to the A site. Site-directed replacements of key residues increased the nucleotide concentrations needed for 50% inhibition and in some cases perturbed synergism. Mutations in either of the nucleotide sites perturbed function at both sites, supporting the important role of synergism.
Adenosine Diphosphate↗
Role of nonrandomly oriented cell division in shaping and bending of the neural plate.
Neural plate shaping and bending are crucial to the process of neural tube formation. Shaping requires intrinsic forces generated by alterations in neuroepithelial cell behavior, whereas bending requires similar intrinsic forces and extrinsic forces generated by alterations in cell behaviors outside the neural plate. This study evaluates the role of nonrandomly oriented cell division in neural plate shaping and epidermal ectoderm expansion during bending by examining mitotic spindle orientation in the neuroepithelium and epidermal ectoderm throughout neurulation. Neuroepithelial mitotic spindles are oriented preferentially in the rostrocaudal plane, suggesting a role for nonrandomly oriented (i.e., rostrocaudal) neuroepithelial cell division in longitudinal lengthening of the neural plate during shaping. Epidermal ectoderm mitotic spindles are oriented preferentially in both rostrocaudal and mediolateral planes, suggesting a role for nonrandomly oriented cell division in epidermal ectoderm elongation and expansion. In neural plate and epidermal ectoderm isolates separated prior to shaping and bending, mitotic spindles continued to be oriented preferentially in the rostrocaudal plane; however, a preferential mediolateral mitotic spindle orientation could not be demonstrated in the epidermal ectoderm isolates. We conclude that the nonrandom rostrocaudal orientation of cell division in the neuroepithelium and epidermal ectoderm is an autonomous process, occurring in the absence of forces from adjacent tissues, whereas the nonrandom mediolateral orientation of cell division in the epidermal ectoderm is dependent upon interactions with the neural plate.
Animals↗
Ion selectivity in the Chlamydomonas reinhardtii flagellar regeneration system.
Extracellular Ca2+ mediates the cellular and molecular responses to cell stimulation of Chlamydomonas reinhardtii. Extracellular Ca2+ concentrations ([Ca2+]e) must exceed certain threshold values to support flagellar excision by acid shock and to stimulate flagellar outgrowth following mechanical shear of the flagella. Also, the magnitude and duration of flagellar RNA accumulations following acid shock or mechanical shear increase with increasing [Ca2+]e. To better understand the role of Ca2+ in flagellar excision, RNA induction, and outgrowth, we have performed a survey of the ion selectivity of each of these responses to acid shock. We found that flagellar excision in vivo following acid shock was supported by Sr2+ and Ca2+, but no other ion tested. LaCl3 and neomycin prevented flagellar excision following acid shock of cells in Ca2+- or Sr2+-containing buffer. Sr2+ addition to detergent-permeabilized cell models, however, failed to elicit flagellar excision in vitro. Cells failed to regrow flagella following flagellar excision in Sr2+-containing buffer unless exogenous Ca2+ was added. Flagellar RNA accumulations of lower magnitude and shorter duration were measured in cells acid-shocked in Sr2+-containing buffer than in Ca2+-containing buffer. These results demonstrate that a Sr2+ influx can evoke flagellar excision following acid shock, but cannot directly activate the machinery for flagellar excision, suggesting that a Sr2+ influx induces excision by stimulating an intracellular Ca2+ release. Furthermore, they suggest that flagellar outgrowth and normal flagellar RNA induction have a strict requirement for Ca2+, which is not satisfied by the proposed intracellular Ca2+ release.
Acids↗
Epidermal ectoderm is required for full elevation and for convergence during bending of the avian neural plate.
Previous studies suggest that bending of the neural plate requires the juxtaposition of neural plate and non-neuroepithelial tissues. The current study examines the role of one of these tissues, the epidermal ectoderm, in bending. Chick blastoderms were harvested from fertile eggs incubated for 24 hr and cultured dorsal-side-up on agar-albumen substrates. In one experiment, a rectangular flap of epidermal ectoderm on one side of each blastoderm was separated from underlying layers and gently reflected onto the area opaca; a fragment of tungsten wire was placed on top of the flap to hold it down and to prevent healing. Embryos were then allowed to develop in a humidified incubator for 2-18 hr. Asymmetric neurulation was observed between the operated and control sides as early as 2 hr after surgery. The amount of asymmetry was quantified in serial transverse sections from embryos collected 8 hr after surgery. Elevation of the lateral edge of the neural plate on the operated side averaged one half to two thirds of that on the control side, and convergence of the operated side around the dorsolateral hinge point toward the dorsal midline did not occur. These results demonstrate that epidermal ectoderm is required for full elevation and for convergence during bending. In another experiment, lateral epidermal ectoderm was removed, leaving only a medial strip consisting of both the epidermal component of the future neural fold and flanking future epidermis. This experiment revealed that although epidermal ectoderm is necessary for full elevation and for convergence of the neural folds, a medial strip of epidermal ectoderm is sufficient to drive bending. Collectively, these results further support the idea that neurulation is a multifactorial process driven by both intrinsic and extrinsic factors acting in concert.
Animals↗
Molecular detection of a B cell clone in a case of PTCL in the absence of T cell clonality.
In this paper we document a case of peripheral T cell lymphoma (PTCL) that exhibited variable T cell histology at presentation and follow-up. Southern blot analysis for T cell receptor (TCR) and immunoglobulin (Ig) receptor gene rearrangements failed to reveal clonal T or B cell populations. TCR gamma (TCRG) and beta (TCRB) chain gene polymerase chain reaction (PCR) amplification of DNA isolated from biopsies was also consistent with polyclonal T cell populations, however Ig PCR revealed clonal Ig rearrangements in follow-up biopsies but not in the presentation biopsy. There was no histological evidence for a neoplastic B cell population in these biopsies although occasional EB virus positive blasts were present. The significance of a cryptic B cell clone is unknown but suggests a relationship with the proliferating polyclonal T cells in this case of PTCL. These data reflect the complexity of PTCL with implications for treatment and patient management.
Aged↗
Design and analysis of epidemiological studies of excess cancer among children exposed to Chernobyl radionuclides.
Within the last decade, a substantial amount of attention has been devoted to etiological research on the association between exposure to fallout radionuclides from the Chernobyl accident and radiation-induced late effects (cancer) among children. A majority of the studies completed to date have been of the descriptive type, which only correlate average population exposure with average rate of cancer incidence as a function of calendar period. Since individual dosimetry is not performed in descriptive studies, it is unclear whether exposure precedes the development of cancer and a final decision cannot be made regarding the association between radiation exposure and cancer. This paper reviews the background epidemiology and outlines an analytical study design that is needed to clarify the unclear association between Chernobyl fallout exposure and childhood cancer. We discuss the essential elements of an analytical case-control design such as genetic predisposition, vital statistics, sample size and power determinations, ascertainment of cases and controls, and phenomenological dose modeling to establish individual doses. Examples such as cytogenetic biodosimetry, medical radiation dosimetry, and cytogenetic characterization of leukemia to minimize exposure and diagnostic misclassification are provided. We recommend the analytical methods described in this paper for studying the role of Chernobyl radionuclides and development of childhood cancer.
Adolescent↗
The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study.
OBJECTIVE: To identify the minimum effective single oral dose of metronidazole for trichomoniasis. METHODS: Women attending an inner-city sexually transmitted disease clinic who had Trichomonas vaginalis vaginitis diagnosed by microscopy were recruited for this randomized, double-blind study. Subjects were given a 0.5-, 1-, 1.5-, or 2-g single oral dose of metronidazole, taken under direct observation. Demographic information, symptoms, and clinical findings were collected from patient interviews, and physical examinations were conducted at the time of enrollment and at the follow-up visit. The primary outcome measure was treatment success at the follow-up visit, established by negative culture and microscopy. RESULTS: Three (1.8%) of the 167 women enrolled were excluded because of vomiting after taking metronidazole, and 66 (40%) of the 164 remaining subjects did not return for the follow-up visit. No associations were found between the proportion of subjects lost to follow-up and the characteristics of these subjects across assignment groups. The treatment success ratio was highest in subjects who received the 1.5-g dose (23, 85%), followed by the 2-g (16, 84%), 1-g (18, 62%), and the 0.5-g dose (8, 35%). CONCLUSION: A single 1.5-g dose of metronidazole has efficacy equivalent to a single 2-g dose for the treatment of T vaginalis vaginitis.
Administration, Oral↗
Neurulation: coming to closure.
Neurulation is a morphogenetic event par excellence. During this highly choreographed four-dimensional process, a flat sheet of ectoderm is transformed into an elongated tubular rudiment, the neural tube, which exhibits rostro-caudal and mediolateral regionalization. Many tissues interact during neurulation to induce and regionalize the neuroectoderm and to produce the morphogenetic forces that drive neurulation. Such forces are generated by fundamental cell behaviors such as changes in cell shape, position and number. In addition, morphoregulatory molecules expressed during neurulation underlie induction and patterning of the forming neuraxis. Despite recent advances in our understanding of neurulation, neural tube defects continue to be a major health care concern. Further research, utilizing a panoply of approaches, is necessary to resolve this issue. Thus, although we are beginning to come to closure in terms of understanding the cellular and molecular mechanisms responsible for normal neural tube formation, 'coming to closure' is exactly the problem that requires resolution to prevent these devastating birth defects.
Animals↗