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Quasielastic neutron scattering experiments performed on yeast phosphoglycerate kinase in the native form and denatured in 1.5 M guanidinium chloride reveal a change in the fast (picosecond time scale) diffusive internal dynamics of the protein. The momentum and energy transfer dependences of the scattering for both states are fitted by an analytical model in which, on the experimentally accessible picosecond time scale and angstrom length scale, the dynamics of a fraction of the nonexchangeable hydrogens in the protein is described as a superposition of vibrations with uniform diffusion in a sphere, the rest of the hydrogens undergoing only vibrational motion. The fraction diffusing changes, from approximately 60% in the native protein to approximately 82% in the denatured protein. The radius of the sphere also changes slightly, from approximately 1.8 A in the native protein to approximately 2.2 A in the denatured protein. Possible implications of these results for the general protein folding problem are discussed.

Ad libitum ingestive behavior of rats with area postrema lesions (APX) was monitored electronically every 6 s for 23 hr. Whereas control rats ate on average 32.2 g of food each day in 16.3 distinct bouts, rats with APX ate comparable amounts of food (28.6 g) in much fewer daily bouts (5.8) that were very large. Controls drank 38.4 ml of water daily in 17.8 bouts, whereas rats with APX consumed more than twice as much water (101.5 ml) in a similar number of bouts (18.5). Controls drank 5.3 ml of 0.5 M NaCl daily in 7.0 bouts, whereas rats with APX consumed 9 times as much saline (45.5 ml) in more bouts (18.2) that were relatively large. These and other results suggest that the area postrema plays an important role in detecting inhibitory signals generated by food or fluid intake and that feeding and drinking bouts may increase in size after APX, because the feedback inhibition provided by those signals is diminished.

We report two unrelated patients with Asymmetric Crying Facies (ACF) and 22q11 deletion. In the first case ACF was the presenting feature. Fluorescent In Situ Hybridization (FISH) revealed 22q11 deletion and subsequent echocardiography demonstrated a normal cardiovascular system. The second presented with hypoparathyroidism, shown on FISH to be secondary to 22q11 deletion. Echocardiography was normal and ACF was found incidentally. Deletion of 22q11 has been reported with ACF occurring as part of the Cardiofacial syndrome (CFS) [Giannotti A, Mingarelli R, (1994): Am J Med Genet 53: 303-304] but this is the first report of ACF with 22q11 deletion in the absence of cardiac abnormalities. A review of the literature pertaining to ACF is presented.

It is now well established that the biological activity of proteins is related not only to their mean molecular structure but also to their intramolecular mobility [1]. In many areas of molecular biology, such as muscle contraction or conformational changes in allosteric proteins, motion is self-evidently crucial. In facilitating such processes as the access of ligands to protein binding sites or in accomodating the change in protein and substrate ge­ometries associated with an enzyme reaction, molecular motion is required.

L-2-Chloropropionic acid (L-CPA), when orally administered at single high dose to rats produces a selective lesion in the cerebellum involving destruction of a high proportion of granule cells by a mechanism which involves N-methyl-D-aspartate (NMDA) receptors. Receptor binding studies demonstrated that L-CPA a had low affinity at the glutamate and glycine binding sites at NMDA receptors (530-660 microM), respectively, whereas L-CPA did not displace [3H]AMPA, [3H]NBQX or [3H]kainate from AMPA or kainate receptors. Whole cell-patch clamp experiments using cultured granule cells failed to demonstrate changes in membrane potential of cultured granule cells when either L-CPA (0.25 or 1 microM) was added alone to the bathing solution, or in combination with glycine (10 microM). Furthermore L-CPA did not alter the magnitude of the inward current produced by application of NMDA (100 microM)) to cultured granule cells, in the presence of glycine, as measured by patch clamp techniques. Experiments were also performed to discover whether L-CPA may alter the release of the excitatory amino acids from the cerebellum, which may then indirectly alter activity at glutamate receptors, leading to neuronal cell death. L-CPA (2 mM) did not affect either basal or stimulated (electrical or high potassium) endogenous aspartate release from superfused cerebellar slices nor did it alter the basal or stimulated release of [3H]aspartate from preloaded slices when introduced into the superfusion medium over 30 min. However, when cerebellar slices were preincubated with 2 mM L-CPA for 2 h at concentrations that are known to be neurotoxic to the brain in vivo, but not in vitro, the stimulated endogenous glutamate and aspartate net release was significantly attenuated, as compared to controls. Basal release was not significantly affected by the introduction of L-CPA-induced cerebellar neurotoxicity may be related to the inhibition of excitatory amino acid release from the cerebellum. In conclusion, although L-CPA does not appear to directly alter NMDA receptor activity the L-CPA-induced cerebellar neurotoxicity may be related to the inhibition of excitatory amino acid release from the cerebellum.

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood sample 2 wk after the first collection from a subset of children (n = 23) who consumed their habitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26% and 24% of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoxanthin, constituted 51% of median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentration indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrations determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-carotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggests both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or = 2 wk without significant bias.

A study of children (2-8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed.The three methods of assessing vit A status were: RDR test, fasting serum retinol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined.Inadequate vit A status was indicated for 17% of subjects by the RDR test (14% cutoff), for 24% by fasting serum retinol concentration (0.87 mumol/L), and for 49% by "abnormal" CIC score. Retinyl esters constituted 24% of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regression tree analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of 0-hour retinyl ester concentration.The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for vit A deficiency. Increased concentrations of retinyl esters at 5 hours compared to those at 0 hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of 0-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect the RDR test.

Numerous epidemiological studies support a strong inverse relationship between consumption of carotenoid-rich fruits and vegetables and the incidence of some degenerative diseases. One proposed mechanism of protection by carotenoids centers on their putative antioxidant activity, although direct evidence in support of this contention is limited at the cellular level. The antioxidant potential of beta-carotene (BC) and lutein (LUT), carotenoids with or without provitamin A activity, respectively, was evaluated using the human liver cell line HepG2. Pilot studies showed that a 90-min exposure of confluent cultures to 500 mumol/L tert-butylhydroperoxide (TBHP) at 37 degrees C significantly (P0.05) increased lipid peroxidation and cellular leakage of lactate dehydrogenase (LDH), and decreased the uptake of 3H-alpha-aminoisobutyric acid and 3H-2-deoxyglucose. Protein synthesis, mitochondrial activity and glucose oxidation were not affected by TBHP treatment, suggesting that the plasma membrane was the primary site of TBHP-induced damage. Overnight incubation of cultures withor = 1 mumol/L dl-alpha-tocopherol protected cells against oxidant-induced changes. In parallel studies, overnight incubation of HepG2 in medium containing micelles with either BC or LUT (final concentrations of 1.1 and 10.9 mumol/L, respectively), the cell content of the carotenoids increased from0.04 to 0.32 and 3.39 nmol/mg protein, respectively. Carotenoid-loaded cells were partially or completely protected against oxidant-induced changes in lipid peroxidation, LDH release and amino acid and deoxyglucose transport. These data demonstrate that BC and LUT or their metabolites protect HepG2 cells against oxidant-induced damage and that the protective effect is independent of provitamin A activity.

We present results of structural modeling of the variable fragment of M alpha 2,3, an antibody capable of neutralizing all short snake toxins. Three different methods were used to model the hypervariable loops: the conformational search algorithm CONGEN (Bruccoleri and Karplus, Biopolymers 26:137-168, 1987), high-temperature molecular dynamics (Bruccoleri and Karplus, Biopolymers 29:1847-1862, 1990), and a combined knowledge-based and energy-based algorithm (Martin et al., Proc. Natl. Acad. Sci. USA 86:9268-9272, 1989). Ninety plausible conformations were generated and were clustered into 13 classes. The clustering results indicate that there was little overlap of the conformational space explored by the different methods. Canonical loop structures were found by all methods for two of the loops, in agreement with previously established empirical modeling criteria. Nine of the 13 classes of structure were rejected on the ground of their lacking common features of antibody combining-site structure. The remaining four models were refined using restrained molecular dynamics. It was found that interconversion between the four resulting structures is possible with no significant energy barriers, suggesting that they are in thermodynamic equilibrium at 300 K. Features of the combining-site structure likely to be particularly important for antigen binding are discussed.

Photoperiodic regulation of the melatonin rhythm was studied in juvenile Djungarian hamsters to test the hypothesis that magnetic field (MF) exposures disrupt sexual maturation. Juveniles in long or short days postweaning were exposed each day to a 1-gauss 60-Hz MF (15 min, 2 h before lights-off). At age 25 days, nighttime duration of the melatonin rise in the pineal gland and circulation of sham-treated controls (adjacent coil system but without current) was8 h in long-day juveniles and nearly 13 h in short-day hamsters. This is the first study in juveniles to demonstrate that the melatonin rhythm duration is regulated by photoperiod and that reproductive development was not disrupted by daily or acute MF exposures; puberty was initiated in long days but arrested by short days, irrespective of MF treatment. In a replicate study, MF exposures had no effect on the duration of increased melatonin. In the initial and the replicate study, amplitude differences in the nighttime pineal or serum melatonin rise possibly reflected inherent variability in repetitive melatonin rhythms. In addition, effects of daily melatonin injections to arrest puberty were not blocked by daily MF exposures. The findings support the conclusion that MF exposures fail to disrupt photoperiodic time measurement or the neuroendocrine mechanism regulating reproductive maturation in the juvenile Djungarian hamster.

We have determined the solution structure of the C-terminal SH2 domain of the p85 alpha subunit of human phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) in complex with a phosphorylated tyrosine pentapeptide sequence from the platelet-derived growth factor receptor using heteronuclear nuclear magnetic resonance spectroscopy. Overall, the structure is similar to other SH2 domain complexes, but displays different detail interactions within the phosphotyrosine binding site and in the recognition site for the +3 methionine residue of the peptide, the side chain of which inserts into a particularly deep and narrow pocket which is displaced relative to that of other SH2 domains. The contacts made within this +3 pocket provide the structural basis for the strong selection for methionine at this position which characterizes the SH2 domains of PI3-kinase. Comparison with spectral and structural features of the uncomplexed domain shows that the long BG loop becomes less mobile in the presence of the bound peptide. In contrast, extreme resonance broadening encountered for most residues in the beta D', beta E and beta F strands and associated connecting loops of the domain in the absence of peptide persists in the complex, implying conformational averaging in this part of the molecule on a microsecond-to-millisecond time scale.

Over a period of 7 years the Toxicology Diagnostic Laboratory at the Onderstepoort Veterinary Institute investigated 370 suspected incidents of poisoning of wildlife. A diagnosis was made in 166 of the outbreaks. Synthetic organic pesticides were responsible for 82.5% of the poisonings. More than 90% of the poisonings were maliciously intended and monocrotophos was the chemical most often used. The data were derived from authenticated outbreaks of poisoning and indicate the chemicals most often incriminated in acute poisoning of wildlife. Of all wild animals, birds are the most frequent victims of poisoning. Uncommon toxicities such as ionophore, cardiac glycoside poisoning and chronic fluorosis are also described.

From 1980 through 1992, the number of legal induced abortions reported to the CDC remained stable, varying each year byor = 5%.This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1992. This report also includes recently reported abortion-related deaths for 1988-1991 and an update on abortion-related deaths for 1985-1987.For each year since 1969, CDC has compiled abortion data received from 52 reporting areas (i.e., the 50 states, the District of Columbia, and New York City).In 1992, 1,359,145 abortions were reported--a 2.1% decrease from 1991. The abortion ratio was 335 legal induced abortions per 1,000 live births, and the abortion rate was 23 per 1,000 women 15-44 years of age. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most had had no previous live births and were obtaining an abortion for the first time. More than half (51%) of all abortions were performed at or before the 8th week of gestation, and 87% were before the 13th week. Approximately 14% of abortions were performed ator = 6 weeks of gestation, 15% were performed at 7 weeks of gestation, and 22% at 8 weeks of gestation. Younger women (i.e., womenor = 19 years of age) were more likely to obtain abortions later in pregnancy than were older women. Sixteen deaths in 1988, 12 deaths in 1989, and five deaths in 1990 were associated with legal induced abortion. The case-fatality rates for 1988, 1989, and 1990, respectively, were 1.2, 0.9, and 0.3 abortion-related deaths per 100,000 legal induced abortions.Since 1980, the number and rate of abortions have remained relatively stable, with only small year-to-year fluctuations ofor = 5%. However, since 1987, the abortion-to-live-birth ratio has declined; in 1992, the abortion ratio was the lowest recorded since 1977. More pregnant women have been opting to carry their pregnancies to term rather than choosing to have an abortion. As in previous years, deaths associated with legal induced abortions occurred rarely (i.e., one or fewer deaths per 100,000 legal induced abortions).The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that efforts to prevent unintended pregnancy can be assessed and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.

Seryl t-RNA synthetase of the bacterium Thermus thermophilus contains a long arm, consisting of an antiparallel coiled coil, that is involved in binding of tRNA. Two crystallographic structures exist for this protein, in which the arm is in different conformations. Here, we use computational methods employing an empirical potential energy function to investigate the flexibility of the long arm. A conformational pathway is calculated between the 2 crystallographic structures using a method based on molecular dynamics simulation. The pathway is analyzed in terms of sequential phi and psi backbone angle changes. Several transient phi and psi displacements are present along the pathway that are not visible in the end states and may be required for transition between them. Energy maps are constructed by rotating the arm around its principal axes of inertia and energy minimizing. The map identifies 2 regions of relatively low energy which might be accessible to the arm.

Objective To compare the results of contact laser vaporization and transurethral resection of the prostate (TURP) in a double-blind randomized controlled clinical trial. Patients and methods The study comprised 148 patients with clinical benign prostatic hypertrophy (BPH) who were recruited and allocated randomly to undergo either TURP (72 patients) or laser ablation of the prostate (76 patients). The outcome was assessed using the American Urological Association (AUA −7) symptom score after 1 and 3 months as the primary measure and by urinary flow rates, haematological factors and the duration of hospital stay and length of catheterization. Results With 90% statistical power, the results at 3 months showed no clinical or statistical difference between the treatments in change in AUA symptom score. A lower blood loss, hospital stay and duration of catheterization significantly favoured the laser treatment, although the failure rate of trial without catheter and the rate of re-operation were higher after laser treatment. Conclusions These early data are encouraging for this technique, although the outcome after one year requires evaluation before advocating the widespread uptake of this method.

The use of hair for the assessment of human mineral nutritional status is controversial, yet has potential because of the ease of collection and storage, and the high concentration of minerals in hair. This study generated baseline values for hair macromineral content in the most commonly used primate model for human nutrition and disease, the rhesus monkey. Hair digests from monkeys in Maryland (n=98) and Puerto Rico (n=208) were analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES). Significant differences existed between the two populations for hair calcium (Ca), magnesium (Mg), and phosphorus (P) (P

To estimate the economic consequences in the United States of routine childhood immunization of children younger than 1 year of age with a rotavirus (RV) vaccine.Cost-effectiveness analysis of a national RV immunization program from the perspective of the health care system and the perspective of society. Estimates of disease incidence, medical expenditures, productivity costs, vaccine efficacy, and vaccine coverage rates were derived from published literature and unpublished vaccine trial reports. The impact of changes in estimates of vaccine efficacy and medical costs was determined by sensitivity analysis.Incremental cost effectiveness, expressed as savings per case of RV diarrhea prevented.Given a vaccine efficacy rate of 50% and a vaccine cost of $30 per dose, an RV immunization program would prevent more than 1 million cases of RV diarrhea, 58,000 hospitalizations, and 82 deaths per year. A vaccine program would cost $243 million per year but would yield net savings of $79 million from the perspective of the health care system and $466 million from the perspective of society. The incremental cost effectiveness was a savings of $459 per case prevented from the societal perspective and $78 per case prevented from the health care system perspective. Sensitivity analyses substantiated net savings over a wide range of variables, and cost effectiveness increased with greater vaccine efficacy or decreased vaccine cost.Economic and disease reduction benefits would be realized from the use of an RV vaccine that is partially protective against severe RV diarrhea. These findings suggest that immunization with an RV vaccine would be cost effective and cost saving.

Differentiated monolayer cultures of Caco-2 human intestinal cells were used as a model to examine interactions between various dietary factors related to the intestinal uptake and absorption of nonheme Fe. Caco-2 cells accumulated 91-98 pmol Fe/mg protein from uptake buffer containing 12 nmol of Fe(III)-nitrilotriacetate during a 1-hr incubation at 37 degrees C. Addition of a 10-fold molar excess of inositol hexaphosphate (IP6) and its lesser phosphorylated derivatives (IP3, IP4, and IP5) decreased cellular uptake and transport of Fe from the lumenal compartment. Addition of ascorbic acid (AA) to the solution containing IPs stimulated Fe uptake and transport in a manner dependent upon the ratio of AA to IP and inversely proportional to the degree of phosphorylation of inositol (i.e., IP3 > IP4 > IP5 > IP6). A mixture of essential amino acids had minimal impact on Fe uptake in either the absence or presence of IPs. Cellular acquisition of Fe from solutions containing IPs was further enhanced by simultaneous addition of essential amino acids and AA. The stimulatory influence of ascorbic acid on Fe uptake from solutions containing IP6 was associated with an increase in the level of ferrous ion. These data further support the usefulness of Caco-2 cells as a model for investigating the effects of various dietary factors on mineral bioavailability.

Public health surveillance data describing family planning services at Title X clinics and characteristics of women receiving these services during 1991 are contained in this report. These data update previously published information concerning characteristics of women and services at such clinics during 1981.1991.Data characterizing patients and services were reported by family planning clinics to Title X grantees. These data for 1991 were provided by all 75 grantees to CDC's Family Planning Services Surveillance (FPSS) project.In 1991, 4.2 million women received services at Title X clinics. Overall, 69.5% of family planning patients had chosen oral contraceptives as their method of contraception, and 64.7% of patients were at or below the federal poverty level. In addition to information characterizing patients and services at Title X clinics, this report also evaluated current data-collection methods used by Title X grantees. Complexities in the analysis reflected variations in the quality and availability of data, including differences in definitions, data-collection instruments at the clinic level, and data categories.The number and characteristics of family planning patients receiving services at Title X clinics during 1991 were similar to the number and characteristics during 1981. Furthermore, these results underscore the need to improve the quality and timeliness of family planning data and to facilitate program planning and operations at the grantee level.These surveillance findings have been communicated to state family planning administrators and to national Title X program administrators. This information will be used to assess how publicly funded family planning clinics currently contribute to health-care delivery and how these clinics might contribute to a national system of reproductive health-care services in the future.

Differentiated cultures of Caco-2 human colonic cells were used to examine the importance of reduction of nonheme ferric iron, Fe(III), for transport across the brush border surface. Cultures accumulated approximately 100 pmol Fe/(h.mg protein) when 10 mumol Fe(III) as the nitrilotriacetic acid complex (1Fe:2NTA) was added to the apical compartment. Ascorbic acid enhanced cellular acquisition of iron in a dose-dependent manner, with a concentration as low as 8 mumol/L ascorbate increasing iron uptake by 50%. Similarly, the rate of iron transport from the apical to the basolateral compartment increased 5.6- and 30-fold when 100 and 1000 mumol/L ascorbic acid, respectively, were present in the apical chamber. Ascorbate-mediated stimulation of iron uptake was temperature dependent and required the reduction of Fe(III) to Fe(II), because it was inhibited by ascorbate oxidase and chelators of Fe(II). Moreover, Caco-2 cells recycled dehydroascorbic acid to ascorbic acid. Ferricyanide and Fe(II) chelators also partially inhibited iron uptake from a medium devoid of ascorbic acid. Intact Caco-2 cells exhibited a ferrireductase activity on the apical surface that accounted for the majority of iron accumulated by cells incubated in the absence of exogenous reductant. These data suggest that reduction of Fe(III) within the lumen or at the cell surface is required for transfer of this essential micronutrient across the intestinal brush border surface.

The Technology Assessment Committee of the Institute for Clinical Systems Integration (ICSI) draws upon the resources of many different groups and in turn, keeps the groups informed about new medical treatments, devices, and procedures. This new Minneapolis-based technology assessment committee uses a collaborative effort to serve the information needs of many employer groups, patients, providers, and health care organizations in the area. This committee serves as the principal mechanism by which new medical and surgical procedures, devices, and treatments, as well as new applications of old but unproved or doubtful applications of existing technologies are reviewed for medical appropriateness at ICSI (a nonprofit quality improvement organization) and at HealthPartners (a combined staff and group model HMO in Minnesota).

The purpose of this study was to evaluate the effect of pedal cadence methodology on the relationship between power output and time to exhaustion. Twenty-four subjects each performed 12 all-out cycle ergometer tests (four at a constant 60 rpm, four at a constant 100 rpm, and four where they were allowed to select and, within each test, vary their cadence). The parameters of the hyperbolic power-time relationship, AWC (anaerobic work capacity) and CP (critical power), were estimated for each pedal cadence methodology using three regression models: nonlinear power-time, linear work-time, and linear power-time-1. In all cases, R2 was high and standard errors of the estimate of AWC and CP were low. With the two constant rpm methodologies, the estimates of AWC and CP were influenced by the choice of regression model. The estimates of AWC and CP were also influenced by the pedal cadence in the all-out tests. For example, the CP derived from the 100 rpm tests (mean +/- SD: 195 +/- 50 W) was lower (p < 0.05) than the CP from the other methodologies (207 +/- 50 W and 204 +/- 48 W), and the AWC from the variable cadence methodology (16.1 +/- 6.2 kJ) was greater than the AWC from constant rpm trials (14.5 +/- 5.9 kJ and 14.6 +/- 5.7 kJ). It is concluded that pedal cadence methodology influences the parameters of the power-time relationship.

Previous studies have noted the presence of mesenchymal stem cells located within the connective tissue matrices of avian skeletal muscle, dermis, and heart. In these studies, clonal analysis coupled with dexamethasone treatment revealed the presence of multiple populations of stem cells composed of both lineage-committed progenitor mesenchymal stem cells and lineage-uncommitted pluripotent mesenchymal stem cells. The present study was undertaken to assess the distribution of these stem cells in the connective tissues throughout various regions of the body. Day 11 chick embryos were divided into 26 separate regions. Heart, limb skeletal muscle, and limb dermis were included as control tissues. Cells were harvested enzymatically and grown using conditions optimal for the isolation, cryopreservation, and propagation of avian mesenchymal stem cells. Cell aliquots were plated, incubated with various concentrations of dexamethasone, and examined for differentiated phenotypes. Four recurring phenotypes appeared in dexamethasone-treated stem cells: skeletal muscle myotubes, fat cells, cartilage nodules, and bone nodules. These results suggest that progenitor mesenchymal stem cells and putative pluripotent mesenchymal stem cells with the potential to form at least four tissues of mesodermal origin have a widespread distribution throughout the body, being located within the connective tissue compartments of many organs and organ systems. © 1995 Wiley-Liss, Inc.

Maternal consumption during pregnancy of methylmercury (MeHg)-contaminated fish in Japan and of MeHg-contaminated bread in Iraq caused psychomotor retardation in the offspring. Studies in Iraq suggested adverse fetal effects when maternal hair mercury concentrations were as low as 20 ppm. This prospective study involved 131 infant-mother pairs in Mancora, Peru with peak maternal hair MeHg levels during pregnancy from 1.2 ppm to 30.0 ppm, geometric mean 8.3. The MeHg was believed to be derived from marine fish in the diet. There was no increase in the frequency of neurodevelopmental abnormalities in early childhood. The possible role of selenium or other protective mechanisms in marine fish is discussed. This previously unpublished study was conducted between 1981 and 1984. Our report of August 1985 to the funding agencies has been circulated, and the data were presented at the Twelfth International Neurotoxicology Conference in Hot Spring, Arkansas, October 30 to November 2, 1994. The current account has not been modified or updated since 1985. For reference to interim publications on fetal MeHg studies in Iraq and New Zealand see Marsh et al., 1995.

This DataWatch examines an outpatient capitated payment system, in the state of Oregon, designed to enhance community services for persons with chronic mental illness who had repeatedly been hospitalized involuntarily. Special state funds and Medicaid dollars were used to pay providers prospectively on a risk-adjusted basis for the delivery of outpatient mental health services. During the three-year study period clients were able to be discharged from the state hospital. Although the data are not straightforward, capitated clients' use of the state mental hospital seems to have declined somewhat more than that of comparison subjects. Outpatient service use was modest and appeared to have little relationship to a client's level of illness severity. Indeed, it was not possible to predict prospectively these clients' outpatient mental health services expenditures.

Understanding how respiratory oscillations are generated and controlled in the mammalian brainstem requires synthesis of neural function at cellular, synaptic, and network levels. Modeling the respiratory network has entered a new era where simulations incorporating complex cellular properties and network interactions exhibited by respiratory neurons are possible. Given the complexity and unknowns of the real system, there are obvious limitations of the modeling in its present form. Nevertheless, if we are to produce neurobiologically satisfying, mechanistic explanations that synthesize cellular and network phenomena, the modeling approach outlined here should have distinct advantages. The approach allows a close interaction between experimental and computational studies, and will enable simulations with increasing neurobiological realism as additional experimental data becomes available. The modeling summarized here represents the initial stages of establishing a computational framework for storing information about neuron and network properties, and for exploring complex dynamical properties in ways not possible experimentally.

The growth factor activin elicits mesodermal fates when applied to prospective ectodermal cells of the Xenopus blastula stage embryo. Previous experiments with dissoci-ated cells showed that there are at least five different responses separated by closely spaced, sharp dose thresh-olds. Here we investigate this multithreshold activin response further using probes for genes expressed at early gastrula stages, namely Xbra, goosecoid, noggin, Xwnt-8 and Mix.1. We show that initial dose-response profiles are broad and smooth in contrast to the later threshold-bound patterns. For Xbra, goosecoid and noggin, the later expression ranges are subsets of earlier ones. Unexpectedly, Xwnt-8 is initially induced at high doses only, but later appears only in cells that have received a low dose of activin. Keeping the cells dissociated after activin treatment, rather than allowing them to reaggregate, prevents sustained expression of Xbra and Xwnt-8 but allows that of goosecoid and noggin. However, cell contact is required for sharpening the dose-response threshold of goosecoid. Finally, we show that a previously reported dorsoventral prepattern in the animal cap is also cell-contact dependent and it is not required for the multi-threshold response to activin.

We reviewed the clinical courses of children < or = 16 years of age with hereditary hemolytic anemias who were admitted to the University of Mississippi Medical Center for aplastic crisis. Constitutional signs, gastrointestinal complaints, and headache were the most frequent findings. Statistically significant decreases in hemoglobin levels, hematocrit, and reticulocyte counts, but not total white blood cell or platelet counts, were found on admission when compared to other times of determination. For 27 of 49 patients, IgM antibody determinations to human parvovirus (B19) were available, and 15 (56%) had positive values. We conclude that erythroid (but not other) blood cell lines are helpful in establishing a clinical diagnosis, and that both acute and convalescent titers are necessary to assess the immune response to the infection. Physicians should continue to search for agents other than B19 parvovirus in patients in whom B19 antibodies cannot be found.

Estimates of anaerobic work capacity (AWC) were determined in 26 subjects using the critical power concept. AWC estimates were derived using three mathematically equivalent models: nonlinear power-time, linear power-1/time, and linear work-time. We hypothesized that large variability between estimates generated using the three models might reflect systematic error in the data and that large standard errors of estimate (SEE) might reflect random error. Therefore, subjects were grouped according to the variability in the three AWC estimates and according to the magnitude of the SEE of the parameter estimates. Then AWC estimates were compared to a criterion measure of anaerobic capacity, namely maximal oxygen deficit. When variability in the AWC estimates was low (10%), all provided accurate measures of oxygen deficit; also, when SEE were low, estimates were accurate. When variability was high, mean AWC estimates derived using linear models differed from oxygen deficit by over 15%; when SEE were high, mean AWC estimates derived using all models differed from oxygen deficit by over 10%. It is concluded that the accuracy of estimates of anaerobic capacity derived using the critical power concept can best be ensured by accepting values only when all three models provide the same value and/or when the SEE of the AWC estimate is small.

3613^ Background: The value of KRAS mutations as predictive markers of clinical benefit of anti-EGFR antibody therapy in patients with mCRC has been shown in randomized trials. Less is known of the...

In the United States in 1990, there were an estimated 1 million pregnancies and 521,826 births among women ages 15-19 years. Rates of teenage pregnancy and birth rates by state in 1990 exceeded those in most developed countries. An estimated 95% of teenage pregnancies are unintended (i.e., they occur sooner than desired or are not wanted at any time).This report summarizes and reviews surveillance data for pregnancies, abortions, and births among women ages 15-19, 15-17, and 18-19 years reported by CDC for 1980 and 1990.Data for births and abortions were reported to state health departments and other health agencies and sent to CDC. The data from each state included the total number of births and abortions by age and race/ethnicity.Data in this report indicate that pregnancy rates by state among U.S. teenagers ages 15-19 years have changed little since 1980. Moreover, many states have reported increases in birth rates that are probably related to concurrent decreases in abortion rates. Pregnancy rates range from 25 to 75 per 1,000 for 15- to 17-year-olds and from 92 to 165 per 1,000 for 18- to 19-year-olds.States with low rates of teenage pregnancy or birth may have developed and used prevention strategies directed at the needs of both younger and older teenagers; these programs may serve as models for other states where birth rates have remained high or have increased since 1980.CDC will continue to conduct surveillance of and analyze data for pregnancies, abortions, and births among teenagers to monitor progress toward national goals and to assist in targeting program efforts for reducing teenage pregnancy.

Since 1980, the number of legal induced abortions reported to CDC has remained fairly stable, varying each year byor = 5%.This report summarizes and reviews data received by CDC for legal induced abortions obtained in 1990.For each year, CDC compiles abortion data received from 52 reporting areas: 50 states, New York City, and the District of Columbia.In 1990, 1,429,577 abortions were reported--a 2.4% increase from 1989. The abortion ratio for 1990 was 345 legal induced abortions per 1,000 live births, and the abortion rate was 24 per 1,000 women ages 15-44 years. Most women undergoing abortions were young, white, and unmarried; most had had no previous live births and were having the procedure for the first time. Approximately half of all abortions were performed before the 8th week of gestation, and 87% were before the 13th week of gestation. Younger women were more likely to obtain abortions later in pregnancy than were older women.Since 1980, the national number (and rate) of abortions has remained relatively stable, with only small (or = 5%) year-to-year fluctuations. However, since 1984, the national abortion ratio has declined; in 1990, the abortion ratio was the lowest recorded since 1977. Increasing rates of childbearing may account for some of this decline.The number and characteristics of women having abortions are needed from all states to furnish an accurate characterization of legal induced abortion in the United States and to assist efforts to identify and reduce preventable causes of morbidity and mortality associated with abortions.

The role of macrophages in the host immune response against cancers remains uncertain. Since nitric oxide synthesis represents a significant macrophage antitumor mechanism in vitro, we evaluated whether NO was synthesized during the immune response to growing murine skin cancers. NO synthesis was readily detectable in enzymatically dissociated tumors (RD-995 and LR-298) and was inhibited by N omega-monomethyl-L-arginine (MLA) and by macrophage depletion. Nitrosylation of iron-sulfur and heme complexes was observed in these tumors using electron paramagnetic resonance spectroscopy. NO production in the presence of increasing concentrations of MLA correlated inversely with tumor cell proliferation in vitro. To elucidate the role of NO during in vivo tumor progression, tumor-bearing mice were treated with continuous infusions of the nitric oxide synthase inhibitor MLA. MLA-treated mice demonstrated increased growth and delayed rejection of the highly antigenic UV radiation-induced regressor tumor LR-298. These experiments demonstrate that macrophage-derived NO synthesis can contribute to the antitumor immune response in vivo.

Thoracic bio-impedance cardiography was used to study the haemodynamic changes in 28 patients undergoing transurethral prostatectomy (TURP) under either general or spinal anaesthesia. Cardiac output and mean arterial pressure fell with induction of general anaesthesia, whilst mean arterial pressure and systemic vascular resistance fell with induction of spinal anaesthesia. The transthoracic fluid index fell during resection under general anaesthesia, but no significant haemodynamic changes were seen during resection under either anaesthetic. This study suggests that resection has no specific adverse haemodynamic consequences. Spinal anaesthesia may produce less haemodynamic disturbance than general anaesthesia in patients undergoing TURP and formal comparison of the 2 techniques seems necessary.

The present experiments describe a marked nycthemeral rhythm in both the appetite for 0.3 M NaCl solution and components of the renin-angiotensin-aldosterone axis stimulated in Sprague-Dawley rats by chronic administration of enalapril, an angiotensin I-converting enzyme inhibitor. Continuous recording of water, NaCl, and food intakes shows that the sodium appetite is manifest as discrete bouts of salt ingestion in temporal proximity to meals and is partially independent of water bouts. In particular, salt bouts occur without water bouts in the late afternoon of a 12:12-h light-dark cycle and continue periprandially with water bouts during the night. Intake of all three commodities is minimal in the morning. In a second experiment, it was determined that plasma renin activity (PRA) was maximally elevated by chronic enalapril in the daytime and that plasma aldosterone was reduced by enalapril but continued to show nycthemeral rhythm peaking in the afternoon. The concurrent maxima in PRA and aldosterone in the afternoon in enalapril-treated rats thus coincides with NaCl intake in the absence of water intake.

Summary— The mobile lithotriptor is a new method of providing extracorporeal shock wave lithotripsy (ESWL) directly to the smaller urological centres. The unit, containing a Dornier HM4 lithotriptor, has treated 135 patients with a total of 168 treatments in 2 centres in the Oxford region. The overall success rate was 87% with no serious morbidity or mortality. The results compare well with the results from larger centres and the system is cost-effective. We suggest that it is one of the best methods of providing ESWL to the smaller urological centres.

Summary— Of 382 patients undergoing prostatectomy in Oxford in 1985 the prevalence of renal impairment (defined as plasma urea > 14 mmol/l or plasma creatinine >200 μmol/l) was 8%; prostatectomy patients had significantly higher plasma ureas than age–matched patients undergoing herniorrhaphy and cholecystectomy in the same hospitals in the same year. A review of the case records of men with renal impairment showed that case history could not predict renal impairment. Although few case notes gave follow-up information, it was evident from the information available that recovery of renal function after prostatectomy did not occur invariably. Renal impairment in men undergoing prostatectomy represents substantial and unrecognised morbidity.

The purpose of this study was to evaluate effects of gender on anaerobic and aerobic contributions to high-intensity exercise. A group of 38 subjects (22 women, 16 men) performed modified Wingate tests against resistances of 0.086 kg kg-1 body mass (0.844 N kg-1) for women and 0.095 kg kg-1 body mass (0.932 N kg-1) for men. The aerobic contribution to total work performed was determined from breath-by-breath analyses of expired gases during each test. Total work in 30 s was 30% lower (Student's t test; P < 0.01) in women than men (211 +/- 5 J kg-1 versus 299 +/- 14 J kg-1). Aerobic contribution was only 7% lower (P = 0.12) in women than men (53 +/- 1 J kg-1 versus 57 +/- 2 J kg-1). The anaerobic component of the work performed, determined by subtraction of the aerobic component from total work in 30 s, was 35% lower (P < 0.01) in women than men (158 +/- 5 J kg-1 versus 242 +/- 15 J kg-1). It is concluded that, because women provide a relatively higher (P < 0.01) portion of the energy for a 30-s test aerobically than men (25% versus 20%), total work during a Wingate test actually underestimates the gender difference in anaerobic capacity between women and men.

Publisher Summary A number of methods have been employed to investigate the absorption of carotenoids in humans. The most common has been the acute or chronic dosing of a carotenoid, such as β-carotene, and the measurement of the plasma response. The gastrointestinal lavage technique, wherein the entire gastrointestinal tract of the subject is cleansed of ingesta prior to consumption of the compound or food component whose absorption is being measured, has been reported for assessing the absorption of calcium but more recently was applied for measuring carotenoid absorption in humans. Metabolic balances can provide estimations of the apparent disappearance of various carotenoids from the gut, and therefore provide a crude estimation of the amount absorbed under various experimental conditions, assuming no degradation or microbial synthesis within the gut. The simultaneous measurement of various tissue responses provides valuable information in conjunction with these techniques. The availability of stable isotopes of various carotenoids holds great promise to provide definitive data in the characterization and quantitation of carotenoid absorption in humans.

Since 1980, the number of legal induced abortions reported to CDC has remained stable, varying each year by5%. In 1989, 1,396,658 abortions were reported--a 1.9% increase from 1988. The abortion ratio for 1989 was 346 legal induced abortions/1,000 live births, and the abortion rate was 24/1,000 women ages 15-44 years. The abortion ratio was highest for black women and women of other minority racial groups and for women15 years of age. Overall, women undergoing abortions tended to be young, white, and unmarried; to have had no previous live births; and to be having the procedure for the first time. Approximately half of all abortions were performed before the eighth week of gestation, and 87% were before the thirteenth week of gestation. Younger women tended to obtain abortions later in pregnancy than older women. This report also includes newly reported abortion-related deaths for 1986 and 1987, as well as an update on abortion-related deaths for the period 1978-1985. Ten deaths in 1986 and six deaths in 1987 were associated with legal induced abortion. The case-fatality rate in 1986 was 0.8 abortion-related deaths/100,000 legal induced abortions and 0.4/100,000 in 1987.

A procedure is reported for the selective ammonia chemical ionization of some nitrogen and sulfur heterocycles in petroleum fractions using ion trap mass spectrometry (ITMS). The ion trap scan routine is designed to optimize the population of ammonium reagent ions and eject from the trap (by radio frequency/direct current isolation) electron ionization products formed during reagent ion formation prior to ionization of the sample. The ITMS procedure is compared with standard ion trap detector and conventional quadrupole ammonia chemical ionization for the determination of nitrogen and sulfur heterocycles in gas oil and kerosine samples. Greatly enhanced selectivity is shown for the ITMS procedure by suppression of competing charge-exchange processes.

The prevalence of smoking in Puerto Rican women was estimated on the basis of data from 3,157 women 15 to 49 years of age who had been surveyed in the 1982 Evaluation of Fertility and Family Planning in Puerto Rico. The weighted prevalence was 15.5%, with a 95% confidence interval of 13.8 to 17.1. The prevalence varied by age group, education, marital status, place of residence at age 15, and consumption of alcohol. The prevalence of smoking increased in successive birth cohorts while the mean age at initiation of the habit tended to decline. The data suggest that in Puerto Rico smoking is on the rise among younger women.

To investigate abnormal growth regulation in keloid fibroblasts, responses to phorbol esters were examined. Treatment of quiescent cultures with phorbol 12-myristate 13-acetate (PMA) blocked a normally occurring (20-24 h) peak of serum-stimulated thymidine incorporation in normal and keloid cells. In keloid fibroblasts PMA induced a delayed peak of DNA synthesis. When indomethacin was added with PMA the delayed peak appeared in normal fibroblasts. The ED50 for inhibition of the 20-24-h peak was 1 nM, whereas the delayed peak required a 50-fold-higher PMA concentration. In both cell types PMA induced prostaglandin E2 (PGE2) synthesis, and exogenous PGE2 caused 50% inhibition of the 20-24-h peak. When PMA and indomethacin were added with PGE2 the delayed peak was inhibited 90% in normal fibroblasts, whereas inhibition of keloid cells was the same as with PGE2 alone. Normal and keloid fibroblasts had the same number of phorbol ester binding sites. However, in normal cells, phorbol 12,13-dibutyrate bound with greater affinity, and down-regulation of phorbol ester binding occurred to a greater extent. These findings suggest that altered expression of protein kinase C isozymes or another molecule that binds phorbol esters may play a role in abnormal growth regulation of keloid cells.