Hyperbaric oxygen ameliorates delayed neuropsychiatric syndrome of carbon monoxide poisoning.

OBJECTIVES: Delayed neuropsychiatric syndrome (DNS) is characterized by mental impairment, motor dysfunction, dementia, or psychosis that develops between a few days and weeks after acute carbon monoxide (CO) poisoning. One possible mechanism responsible for CO-mediated encephalopathy involves oxidative stress, such as lipid peroxidation, caused by the cellular uptake of CO and which leads to an inflammatory cascade. There is no current effective treatment for DNS. We applied 8-40 sessions of hyperbaric oxygen therapy (HBO2) to patients with DNS and evaluated its effectiveness. METHODS: After admission, all patients were administered piracetam or bromocriptine, or both, and received HBO2. Neuropsychiatric tests included EEG, mini-mental status examination (MMSE), brain MRI, event-related potential (ERP), and brain perfusion scan (brain SPECT). Results of these tests were compared before and after HBO2, and the clinical features were monitored during this period. RESULTS: The symptoms of DNS for all patients improved significantly after HBOT. Although white matter changes remained evident in the brain MRI scans, other examinations such as EEG, MMSE, ERP, and 99mTc-ECD brain SPECT were nearly normal after HBOT. CONCLUSION: Our results suggest that HBO2 decreases the severity of impairment in patients with DNS. Although a large randomized trial is required to address the efficacy of this therapy, therapeutic application of HBO2 may be recommended in patients with DNS after CO poisoning.

Regulation of a recombinant pea nuclear apyrase by calmodulin and casein kinase II.

A cDNA encoding a pea nuclear apyrase was previously cloned. Overexpressions of a full-length and a truncated cDNA have been successfully expressed in Escherichia coli BL21(DE3). The resulting fusion proteins, apyrase and the C-terminus (residues 315-453) of apyrase, were used for calmodulin (CaM) binding and phosphorylation studies. Fusion protein apyrase but not the C-terminus of apyrase can be recognized by polyclonal antibody pc480. This suggested that the motif recognized by pc480 was located in the N-terminal region of apyrase. The recombinant apyrase protein also showed an activity 70 times higher than that of endogenous apyrase using ATP as a substrate. The recombinant apyrase has a preference for ATP more than other nucleoside triphosphate substrates. CaM can bind to recombinant apyrase, but not to the C-terminus of apyrase. This implies that the CaM-binding domain must be in the first 315 amino acids of the N-terminal region of apyrase. We found that one segment from residue 293 to 308 was a good candidate for the CaM-binding domain. This segment 293 FNKCKNTIRKALKLNY 308 has a basic amphiphilic-helical structure, which shows the predominance of basic residues on one side and hydrophobic residues on the other when displayed on a helical wheel plot. Using the gel mobility shift binding assay, this synthetic peptide was shown to bind to CaM, indicating that it is the CaM-binding domain. Both recombinant apyrase and the C-terminus of apyrase can be phosphorylated by a recombinant human protein kinase CKII. Phosphorylation does not affect CaM binding to recombinant apyrase. However, CaM does inhibit CKII phosphorylation of recombinant apyrase and this inhibition can be blocked by 5 mM EGTA.

Dehydroepiandrosterone sulfate (DHEAS) suppresses P2X purinoceptor-coupled responses in PC12 cells.

Some steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels in addition to their well-known genomic effects via intracellular steroid receptors. Such effects were found in GABA receptor, nicotinic receptors, yet not investigated in P2X purinoceptors. In this study, the effects of dehydroepiandrosterone sulfate on the P2 purinoceptor was investigated. Results show that dehydroepiandrosterone sulfate acutely inhibits P2X purinoceptor functions in PC12 cells. Dehydroepiandrosterone sulfate suppressed ATP-induced cytosolic free calcium concentration ([Ca(2+)](i)) rise, cytosolic free sodium concentration ([Na(+)](i)) rise, and dopamine secretion in the presence of external calcium, but had no effect on ATP-induced [Ca(2+)](i) rise in the absence of external calcium or on UTP-induced [Ca(2+)](i) rise in the absence or presence of external calcium. Our data show that dehydroepiandrosterone sulfate exerted its effect on P2X, but not on the P2Y purinoceptors found in PC12 cells. Estradiol and estrone have similar effects on P2X purinoceptor, but dehydroepiandrosterone and progesterone do not.

Fetal death rate in the United States, 1979-1990: trend and racial disparity.

OBJECTIVE: To examine the impact of changes in birth weight distribution in individual groups and in birth weight-specific fetal death rates on the decline in the crude fetal death rate in the United States. METHODS: Data on live births and fetal deaths in the U.S. for the period 1979-1990 were examined by birth weight group and race using Kitagawa's method for analysis of the crude fetal death rate. RESULTS: In the period 1979-1990, all racial groups had a decrease in the crude fetal death rate, more so in whites and others (about 22%) than in blacks (10%). In the white population, 73.4% of the total reduction in the crude fetal death rate was attributable to the improvement in birth weight-specific fetal death rates, and the remaining portion of the reduction was due to a favorable change in birth weight distribution. In the black population, the reduction in the crude fetal death rate was entirely attributable to the improvement in the birth weight-specific fetal death rates. However, in other groups, a favorable change in the birth weight distribution was the major determinant. Although black births represented 16.5% of all births in the U.S., they accounted for 26-29% of the crude fetal death rate. Disparity in the crude fetal death rates for blacks and whites is explained almost entirely by differences in birth weight distribution. CONCLUSIONS: A further decrease in the crude fetal death rate in the U.S. requires a decrease in low birth weights, particularly in blacks.

Relationship of cesarean delivery to lower birth weight-specific neonatal mortality in singleton breech infants in the United States.

OBJECTIVE: The preferred route of delivery for breech presentation has been controversial. We compared the birth weight-specific neonatal mortality of vaginal births to cesarean births in singleton births with breech presentation. METHODS: A total of 371,692 singleton live births with breech presentation were selected for the study from the United States birth cohorts for the years 1989-1991. Differences in birth weight specific mortality were compared using a z-statistic for differences in proportions and by logistic regression. RESULTS: Compared to primary vaginal births, primary cesarean births had significantly lower neonatal mortality for all birth weight groups, despite increased prevalence of fetal malformations in the cesarean as compared with vaginally delivered group. This mortality difference was greatest in the first hour of life. Difference in overall neonatal (less than 28 days) mortality rate ranged from a low of 1.6-fold in the 500-749 g group (726.6 per 1000 vaginal births compared with 456.3 per 1000 cesarean births, P < .001) to as high as about three-fold in the 1250-1499 g group (232.9 per 1000 vaginal births compared to 72.5 per 1000 cesarean births, P < .001). In the group with birth weights over 2500 g, neonatal mortality in the primary vaginal births was 5.3 per 1000 and in the primary cesarean births, 3.2 per 1000 (P < .001). Similarly, repeat cesarean births had significantly lower birth weight-specific neonatal mortality, compared with vaginal births after previous cesarean. CONCLUSION: Singleton live births with breech presentation delivered by cesarean had lower birth weight-specific neonatal mortality as compared with vaginal births.

Fetal death in a population of black women.

To describe the clinical causes of fetal death in black women, we performed a record review of the primary causes of fetal deaths (n = 315, > or = 500 g or > or = 24 weeks' gestation) occurring over an 11-year period in a population of 26,852 black women who delivered at the Chicago Lying-in Hospital, University of Chicago Hospitals, Chicago, IL. The over-all fetal death rate (FDR) per 1,000 total births was 11.7, consistent with U.S. vital statistics data for blacks. The FDR per 10,000 births attributed to hypertension was nine times greater in our population than in a historical comparison population of Canadian white women: 19.5 (95% CI = 13.7, 25.4) versus 2.2 (P < .0001), respectively, although the prevalence of hypertension was only 1.2 times greater in the population of black women. Furthermore, hypertension in pregnancy accounted for 15% of the excess fetal mortality in our population of urban black women as compared to the population of Canadian white women. Health care providers should be aware of the risk of fetal death in hypertensive, innercity, U.S. black women.

Dehydroepiandrosterone sulfate inhibition of catecholamine secretion from bovine adrenal chromaffin cells.

Dehydroepiandrosterone sulfate (DHEAS) dose-dependently inhibited [3H]norepinephrine (NE) secretion and the corresponding [Ca2+]i rise induced by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpoperazimium (DMPP) in bovine chromaffin cells. DHEAS at 10 microM, the physiological concentration in human serum, significantly inhibited both the release of [3H]NE and the rise of [Ca2+]i induced by DMPP in chromaffin cells. DHEAS also inhibited the [3H]NE release induced by the Na+ channel activator veratridine. However, DHEAS did not affect either the [3H]NE release, or the corresponding [Ca2+]i rise induced by high K+. Moreover, DHEAS suppressed the [Na+]i rise induced by either DMPP or high K+ as monitored by the fluorescence 340/380 ratio of SBFI loaded chromaffin cells. Our results suggest that the inhibitory effects of DHEAS on secretion mainly occur at nicotinic receptors as well as at the voltage-dependent Na+ channels.

Effects of extracellular ATP on Ca2+ mobilization in Madin Darby canine kidney (MDCK) cells.

Previous studies have demonstrated that ATP activates calcium-dependent K+ channels thereby leading to plasma membrane hyperpolarization and chloride secretion in MDCK cells. However, the signaling pathway involved in regulating ATP-evoked Ca2+ mobilization in MDCK cells remains unclarified. The present study was performed to elucidate the mechanisms underlying ATP-evoked calcium mobilization and inositol phospholipid turnover in MDCK cells. Our results indicate that ATP exerted its effects by activating the P2u subtype purinoceptor because both ATP and UTP but not adenosine caused Ca2+ mobilization. ATP induced [Ca2+]i increase in a dose-dependent manner with a maximal and half-maximal effect at 100 microM and 5 microM, respectively. In the absence of external Ca2+, both UTP and ATP were capable of mobilizing Ca2+ from internal stores through an IP3-sensitive pathway and the response for the former was larger than the latter. While in the presence of external Ca2+, the magnitude of UTP-induced [Ca2+]i increase was similar to that of ATP. These observations suggest that other mechanisms involved in addition to P2u subtype receptors in regulating ATP-induced Ca2+ response. The Ca2+ transients observed in Ma(2+)-depleted media were greater than those seen in Mg(2+)-contained media. ATP-induced Na+ influx were evidenced by SBFI loaded MDCK cells in Mg(2+)-depleted media. These data support that non-selective ATP4-membrane pores were formed under the application of ATP. The ATP-induced Ca2+ rise was suppressed by either omega-conotoxin or La3+ but was unaffected by the L-type Ca2+ channel blockers, verapamil and nifedipine. The deprivation of external Na+ also enhanced the ATP-induced Ca2+ rise. These data indicate that a P2 receptor-mediated cation channel was also involved under the stimulation of ATP.

The Sperm Transfer System in Kinbergonuphis simoni (Polychaeta:Onuphidae).

Tube dwelling Kinbergonuphis simoni (Santos, Day and Rice) achieves a 98.9% fertilization efficiency by means of a sperm transfer system involving spermatophores and seminal receptacles. The spermatophores are mushroom-shaped structures released as clumps. The seminal receptacles are paired sac-like organs embedded in the dorsal epidermis of female genital segments. Males release spermatophores into the environment, and females pick them up with their ventral palps and first pair of parapodia. Stored sperm remain viable for fertilization for at least one month. Spermatophore release and egg laying are independent of the presence of the opposite sex. Advantages associated with this system are discussed, and include asynchronous reproduction, a long breeding season, reduced sperm loss, and reduced exposure to risks. This sperm transfer mode is the first reported in the family Onuphidae and is proposed for other small, tube-dwelling onuphids.

Alterations in the lipids and prostaglandins in mouse spleen following the ingestion of menhaden oil.

Two groups of male mice were fed for 2 weeks with a semisynthetic diet supplemented with either 10% hydrogenated coconut oil or 10% menhaden oil. The spleen from animals fed with menhaden oil contained significantly higher amounts of polyunsaturated n-3 fatty acids. The n-3 fatty acids reciprocally replaced arachidonic acid in the phospholipids. The synthesis of 6-keto prostaglandin F1 alpha and prostaglandin E2 by spleen tissues were significantly depressed (70-80%) in mice consuming menhaden oil. These studies indicated that n-3 fatty acids can effectively displace arachidonic acid from spleen lipids and thereby affect the synthesis of prostaglandins. The implications of these observations are discussed.

Peritoneal macrophages from mice fed dietary (n-3) polyunsaturated fatty acids secrete low levels of prostaglandins.

Peritoneal macrophages from mice fed diets containing 10% menhaden oil incorporated significant amounts of n-3 polyunsaturated fatty acids (n-3 PUFA) into cellular lipids, and this lowered arachidonic acid in these lipid classes compared to those from mice fed diets containing 10% coconut oil. The n-3 PUFA-enriched macrophages secreted significantly smaller amounts of prostaglandin E, thromboxane B and 6-keto-prostaglandin F1 alpha when stimulated with opsonized zymosan or phorbol myristate acetate. These studies demonstrated that menhaden oil-enriched diets influence fatty acid composition and prostaglandin synthesis in macrophages.

Human development index as a predictor of infant and maternal mortality rates.

OBJECTIVE: The United Nations Human Development Index (HDI) is a composite index of life expectancy, literacy, and per capita gross domestic product that measures the socioeconomic development of a country. We estimated infant and maternal mortality rates in the world and assessed how well the HDI and its individual components predicted infant and maternal mortality rates for individual countries. MATERIALS: Data on mortality rates and values for HDI components were obtained from the United Nations and the World Bank. RESULTS: For the 1987 to 1990 period, approximately 9 million infant deaths and 349,000 maternal deaths occurred in the world annually, yielding global infant and maternal mortality rates of 67 per 1000 and 250 per 100,000 live births, respectively. HDI is a powerful predictor of both infant and maternal mortality rates. It accounts for 85% to 92% of the variation in infant mortality rates, and 82% to 85% of the variation in maternal mortality rates among countries. Each component of HDI is also strongly correlated with both infant and maternal mortality rates (significance of all values for r, p < 0.001), and eliminating life expectancy from HDI does not decrease significantly the predictive power of HDI for infant or maternal mortality rates. CONCLUSION: HDI is not only a useful measure for socioeconomic development, but also a powerful predictor of infant and maternal mortality rates for individual countries.

PIP: The UN Human Development Index (HDI), a composite index of life expectancy, literacy, and per capita gross domestic product, provides a measure of a country's level of socioeconomic development. An analysis of mortality data obtained from the United Nations and the World Bank indicated that the HDI is, in addition, a powerful predictor of infant and maternal mortality rates. The 1990 infant mortality rate in the 78 countries for which data were available ranged from 5/1000 live births in Japan to 143/1000 live births in Bhutan and Gambia; the maternal mortality rate ranged from 3/100,000 live births in Finland to 1500/100,000 live births in Nepal. The HDI accounted for 85-92% of the variance in infant mortality rates and 82-85% of that in maternal mortality. Although life expectancy tended to be the HDI component with the strongest predictive power, especially for infant mortality, the explanatory power of the index did not decrease significantly even when this component was excluded. If infant and mortality rates in developed countries in 1987-90 had prevailed worldwide, 8 million infant and 340,000 maternal deaths would have been averted each year.

Cutis verticis gyrata in a neonate.

The primary form of cutis verticis gyrata, a rare skin lesion, is described for the first time in a neonate in whom it was associated with other congenital anomalies. The combination of a histologically normal skin biopsy from the lesion and neurologic deficit supported the diagnosis; follow-up at 7 months of age showed persistent hypotonia and significant developmental delay. Differentiation of primary and secondary forms of cutis verticis gyrata and currently recognized etiologies are also briefly reviewed.

Enzymatic and immunologic quantitation of erythrocyte superoxide dismutase in adults and in neonates of different gestational ages.

Human erythrocyte superoxide dismutase (SOD) was purified and specific antiserum was raised in rabbits. Enzyme preparations from adults and from newborns were shown to be indistinguishable in their immunologic and electrophoretic properties. Erythrocyte SOD was quantitated in blood specimens from adults and in cord blood specimens from neonates of different gestational ages, using both an immunologic and an activity assay. The mean values of SOD concentration and SOD activity for adults and for newborns of average size for gestational age (AGA) showed no significant difference. Adult red cells contained 28.0 +/- 8.3 SOD units/mg hemoglobin (Hgb) whereas AGA neonatal red cells had 28.5 +/- 8.3 SOD units/mg Hgb. Immunologic quantitation by single radial immunodiffusion revealed 0.69 +/- 0.07 micrograms SOD/mg Hgb in adults and 0.70 +/- 0.14 micrograms SOD/mg Hgb in the AGA neonates; however, the SOD concentrations from both small for gestational age (SGA) and large for gestational age (LGA) neonates were significantly lower than those of the AGA neonates and the adults (SGA: 0.57 +/- 0.24 micrograms SOD/mg Hgb, P less than 0.05; LGA: 0.59 +/- 0.16 micrograms SOD/mg Hgb, P less than 0.05).

Short interpregnancy intervals and the risk of adverse birth outcomes among five racial/ethnic groups in the United States.

The authors studied the effects and population-level impact of short (< or = 12 months) interpregnancy intervals on the risks for low (<2.5 kg) birth weight and preterm (<37 weeks) delivery of liveborn singleton infants to US African American, Mexican, Native American, non-Hispanic white, and Puerto Rican mothers (n = 4,841,418) from 1989 to 1991. Statistical analyses were done by using the Mantel-Haenszel correlation statistic chi-square test and logistic regression. The proportion of livebirths associated with < or =12-month interpregnancy intervals was the lowest among non-Hispanic whites (18.5%, 95% confidence interval 18.5-18.5) and the highest among Native Americans (29.7%, 95% confidence interval 29.2-30.2). As compared with mothers with >12-month intervals, mothers with <6-month intervals had an approximately 50% to 80% increased risk of very low (<1.5 kg) birth weight delivery and a 30% to 90% increased risk of very preterm (<32 weeks) delivery. Logistic regression analyses showed that the adverse effects of short intervals were reduced by about 10% but remained for the most part significant after controlling for potential confounding by maternal age, education, parity, marital status, prenatal care, smoking, and previous preterm delivery.

Light-modulated abundance of an mRNA encoding a calmodulin-regulated, chromatin-associated NTPase in pea.

A CDNA encoding a 47 kDa nucleoside triphosphatase (NTPase) that is associated with the chromatin of pea nuclei has been cloned and sequenced. The translated sequence of the cDNA includes several domains predicted by known biochemical properties of the enzyme, including five motifs characteristic of the ATP-binding domain of many proteins, several potential casein kinase II phosphorylation sites, a helix-turn-helix region characteristic of DNA-binding proteins, and a potential calmodulin-binding domain. The deduced primary structure also includes an N-terminal sequence that is a predicted signal peptide and an internal sequence that could serve as a bipartite-type nuclear localization signal. Both in situ immunocytochemistry of pea plumules and immunoblots of purified cell fractions indicate that most of the immunodetectable NTPase is within the nucleus, a compartment proteins typically reach through nuclear pores rather than through the endoplasmic reticulum pathway. The translated sequence has some similarity to that of human lamin C, but not high enough to account for the earlier observation that IgG against human lamin C binds to the NTPase in immunoblots. Northern blot analysis shows that the NTPase MRNA is strongly expressed in etiolated plumules, but only poorly or not at all in the leaf and stem tissues of light-grown plants. Accumulation of NTPase mRNA in etiolated seedlings is stimulated by brief treatments with both red and far-red light, as is characteristic of very low-fluence phytochrome responses. Southern blotting with pea genomic DNA indicates the NTPase is likely to be encoded by a single gene.

FIN219, an auxin-regulated gene, defines a link between phytochrome A and the downstream regulator COP1 in light control of Arabidopsis development.

Light signals perceived by photoreceptors are transduced to negatively regulate COP1, a key repressor of photomorphogenic development. To identify genes involved in light inactivation of COP1, a genetic screen was employed to identify extragenic modifier mutations of a temperature-sensitive cop1 allele. One suppressor mutation isolated also exhibited a far-red-specific long hypocotyl phenotype in a wild-type background. Further phenotypic analyses of this new mutation, named fin219, suggested that it defines a novel phytochrome A signaling component. Genetic analysis indicated that FIN219 interacts closely with another phytochrome A signaling component, FHY1. Molecular characterization of FIN219 indicated that it encodes a cytoplasmic localized protein highly similar to the GH3 family of proteins and its expression is rapidly induced by auxin. In contrast to its loss-of-function mutant phenotype, overexpression of FIN219 results in a far-red-specific hyperphotomorphogenic response. Our data suggest that FIN219 may define a critical link for phytochrome A-mediated far-red inactivation of COP1 and a possible cross-talk juncture between auxin regulation and phytochrome signaling.

Outcome of very low birth weight infants in industrialized countries: 1947-1987.

Neonatal intensive care has led to a progressive improvement in the survival of very low birth weight (VLBW, < 1,500 g) infants. However, it has not been established whether there has been a simultaneous increase or decrease in the prevalence of handicapping conditions in this group of children. To explore this question, a meta-analysis was performed using outcome data of 32 developmental studies of VLBW infants born in industrialized countries between 1947 and 1987. The authors' results show that the proportion of VLBW infants who survived and had an intact outcome progressively increased between 1947 and 1987--from 147 per 1,000 live births in the period 1947-1965 to 498 per 1,000 in the period 1980-1987 (p < 0.01). The prevalence of major handicapping conditions for the subset of VLBW infants who weighed < 1,000 g at birth increased, resulting from the increasing survival rates. However, the prevalence of major handicapping conditions among all children with VLBW decreased from 147 per 1,000 live births in 1947-1965 to 45 per 1,000 in 1980-1987 (p = 0.02). The authors' meta-analysis suggests that improved survival of VLBW infants has not been accompanied by an increase, but more likely a decrease, in the prevalence of handicapping conditions in this birth weight group.

Light regulation of the abundance of mRNA encoding a nucleolin-like protein localized in the nucleoli of pea nuclei.

A cDNA encoding a nucleolar protein was selected from a pea (Pisum sativum) plumule library, cloned, and sequenced. The translated sequence of the cDNA has significant percent identity to Xenopus laevis nucleolin (31%), the alfalfa (Medicago sativa) nucleolin homolog (66%), and the yeast (Saccharomyces cerevisiae) nucleolin homolog (NSR1) (28%). It also has sequence patterns in its primary structure that are characteristic of all nucleolins, including an N-terminal acidic motif, RNA recognition motifs, and a C-terminal Gly- and Arg-rich domain. By immunoblot analysis, the polyclonal antibodies used to select the cDNA bind selectively to a 90-kD protein in purified pea nuclei and nucleoli and to an 88-kD protein in extracts of Escherichia coli expressing the cDNA. In immunolocalization assays of pea plumule cells, the antibodies stained primarily a region surrounding the fibrillar center of nucleoli, where animal nucleolins are typically found. Southern analysis indicated that the pea nucleolin-like protein is encoded by a single gene, and northern analysis showed that the labeled cDNA binds to a single band of RNA, approximately the same size and the cDNA. After irradiation of etiolated pea seedlings by red light, the mRNA level in plumules decreased during the 1st hour and then increased to a peak of six times the 0-h level at 12 h. Far-red light reversed this effect of red light, and the mRNA accumulation from red/far-red light irradiation was equal to that found in the dark control. This indicates that phytochrome may regulate the expression of this gene.