Barriers to prenatal care for low-income women.

Inadequate prenatal care is associated with poor birth outcomes. Recognizing barriers to care is necessary to improve results. Postpartum in-hospital interviews were conducted with women admitted through emergency departments with no physician of record (n = 69) in 8 Sacramento hospitals during April and May 1991. A focus group of local obstetrician-gynecologists was used to determine physicians'' attitudes about caring for low-income women. We undertook the study in response to an increased number of "no doc" births. The inability to find a physician willing to accept them was reported by the women as the single largest barrier to obtaining care, cited by 64% of women overall and 96% of those who tried but were unable to obtain care. Transportation difficulties were a problem regardless of women''s success in obtaining care and were ranked as the top barrier by women who never tried to obtain care. Physicians cited administrative difficulties and reimbursement levels of Medi-Cal plus extra care requirements and resource dependency of low-income patients as barriers to caring for this population. The value ascribed to prenatal care by women and physicians'' perceptions of women''s attitudes about care contrasted sharply. The link between poor women and physicians providing obstetric services can be fragile. The difficulty finding physicians willing to take them indicates that these women need special support services to ensure adequate care during pregnancy.     

Evolution of cow nonstomach lysozyme genes.

Expansion of the lysozyme gene family is associated with the evolution of the ruminant lifestyle in ruminant artiodactyls such as the cow. Gene duplications allowed recombination between stomach lysozyme genes that may have assisted in the evolution of an enzyme adapted to survive and function in the stomach environment. Despite amplification of lysozyme genes, cow tears, milk, and blood are considered to be lysozyme deficient. Here we have identified 2 new cow lysozyme cDNA sequences and show that at least 4 different lysozymes are expressed in cows in nonstomach tissues and probably function as antibacterial defence enzymes. These 4 lysozyme genes are in addition to the 4 digestive lysozyme genes expressed in the stomach, yielding a number of expressed lysozyme genes in the cow larger than that found in most nonlysozyme-deficient mammals. In contrast to expectations, evidence for recombination between stomach and nonstomach lysozyme genes was found. Recombination, through concerted evolution, may have allowed some lysozymes to acquire the ability to survive in occasional acidic environments.     

Ligandin: An adventure in Liverland

Summary Ligandin is an abundant soluble protein which has at 1/2 of 2–3 days, is induced by many drugs and chemicals, and is stabilized in the absence of thyroid hormone. The protein is strategically concentrated in cells associated with transport and detoxification of many endogenous ligands, such as bilirubin, and exogenous ligands, such as drugs and chemicals. The protein is a dimer in rat liver. Whether the dimer is a primary gene product or at least two genes are involved is not known. The protein has broad, low affinity catalytic activity as a GSH-S-transferase for many ligands having electrophilic groups and hydrophobic domains. It catalyzes formation of GSH conjugates, noncovalently binds some ligands prior to their biotransformation or excretion in bile, and covalently binds other ligands, such as activated carcinogens. Recent studies include the possible role of ligandin in chemical carcinogenesis, diagnosis of inflammatory and neoplastic disease of the liver and kidney, and participation in intracellular transport. Although some of the roles that have been outlined are speculative, any single function is important. The GSH-Stransferases are primitive enzymes and non specific binding proteins but it is precisely their simplistic design that allows such protean serviceability.Ligandin illustrates a group of hepatic disposal mechanisms which involve bulk transport of ligands. Although specific uptake and transport mechanisms have been described for several hormones which enter the hepatocyte in small quantities and regulate intermediary metabolism and, possibly, cell maturation, bulk transport of ligands into, through and out of the liver involves mechanisms which accomodate many metabolites, drugs and chemicals of diverse structure. The liver is bathed in sewage which contains what we ingest or are injected with and potentially toxic products of intestinal microorganisms. The chemical formulas of the many substances which are metabolized by the liver provide a horror show of potentially reactive and toxic metabolites, mutagens and carcinogens. Despite this alimentary Love Canal, we and our livers do remarkably well. These hepatic disposal mechanisms, as exemplified by ligandin, evolved in ancient times. They are present, albeit sluggishly, in insects and ancient elasmobranchs. Hepatic uptake and removal mechanisms of high capacity, modest affinity and broad substrate range permit us to live in what has probably always been a threatening world.Abbreviations DAB N,N-dimethyl-4-amino azobenzene - GSH reduced glutathione - BSP bromosulfophthalein - SDS sodium dodecyl sulfate     

Cerebral Metabolic Effects of Monoamine Oxidase Inhibition in Normal and 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Acutely Treated Monkeys

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2-deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP-treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures.     

Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress.

A reduction in immune function has been found in patients with a major depressive disorder and in persons undergoing severe life stress. This study investigated the association between increased sympathetic nervous system activity and reduced natural killer (NK) cytotoxicity in depression and Alzheimer caregiver stress. NK activity and plasma concentrations of epinephrine, norepinephrine, and neuropeptide Y were measured in depressed patients (n = 19) and age- and gender-matched controls (n = 19), and in Alzheimer spousal caregivers (n = 48) and matched noncaregiver controls (n = 17). Plasma levels of neuropeptide Y, but not circulating basal levels of catecholamines, were significantly (P less than 0.01) elevated in the depressed patients and in the caregivers compared with respective controls. NK activity was significantly (P less than 0.001) lower in the depressed patients than in their controls, but not different between the caregivers and the noncaregiver controls. Circulating concentrations of neuropeptide Y, but not catecholamines, were inversely correlated (r = -0.31, P less than 0.001) with NK activity. In addition, multiple regression analyses demonstrated that the significant (P less than 0.01) association between neuropeptide Y and natural cytotoxicity was independent of the relative contribution of age and basal and dynamic levels of epinephrine and norepinephrine. These findings suggest that increased sympathetic nervous system activity and the release of neuropeptide Y may be associated with the modulation of NK cytotoxicity.     

“Active” conformation of an inactive semi-synthetic ribonuclease-S

We have studied the integrity of folded structure of a fully active semi-synthetic ribonuclease-S which lacks amino acid residues 16 through 20, and an inactive one with the same residues deleted and 4-fluoro-l-histidine substituted for active site histidine 12. Using “Y” form crystals, we obtained X-ray structural data to a resolution of 2·6 Å and, incorporating phase information calculated from refined ribonuclease-S coordinates, prepared several types of electron density maps. These showed that the overall backbone structure and active site configuration of both analogues do not differ noticeably from those of the native protein. Structural homology extends to the catalytically relevant side-chain at position 12; 4-F-His² assumes the same position as does His in active ribonuclease-S. This supports the view that the 4-F-Hisl2 analogue is inactive due to a change in histidine 12 imidazole basicity, rather than to any significant conformational distortion within the active site.     

Manganese and Defenses against Oxygen Toxicity in Lactobacillus plantarum

Lactobacillus plantarum is aerotolerant during log-phase growth on glucose, but is an obligate aerobe on polyols. Respiration was cyanide resistant and under certain conditions was associated with the accumulation of millimolar concentrations of H(2)O(2). On glucose, optimal growth was observed in the absence of O(2). Extracts of L. plantarum did not catalyze the reduction of paraquat by reduced nicotinamide adenine dinucleotide, but plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) was readily reduced. Such extracts produced O(2) (-) in the presence of NADH plus plumbagin. Plumbagin caused a 10-fold increase in the rate of respiration of intact cells in the presence of glucose and also imposed a loss of viability which was dependent upon both glucose and O(2). Although extracts of L. plantarum were devoid of true superoxide dismutase activity, this organism was comparable to superoxide dismutase-containing species in its resistance toward hyperbaric O(2) and toward the oxygen-dependent lethality of plumbagin. L. plantarum required Mn-rich media and actively accumulated Mn(II). Soluble extracts were found to contain approximately 9 mug of Mn per mg of protein and 75 to 90% of this Mn was dialyzable. Such extracts exhibited a dialyzable and ethylenediaminetetraacetic acid-inhibitable ability to scavenge O(2) (-). This O(2) (-)-scavenging activity was due to the dialyzable Mn(II) present in these extracts and could be mimicked by MnCl(2). Cells grown in Mn-rich media were enriched in dialyzable Mn and were more resistant toward oxygen toxicity and toward the oxygen-dependent plumbagin toxicity than were cells grown in Mn-deficient media. L. plantarum exhibited no nutritional requirement for iron and little or no iron was present in these cells, even when they were grown in iron-rich media. L. plantarum thus appears to use millimolar levels of Mn(II) to scavenge O(2) (-), much as most other organisms use micromolar levels of superoxide dismutases.     

Modification of cell membrane in variants of chinese hamster cells resistant to abrin

Stable and heritable variants of Chinese hamster ovary (CHO) cells which are resistant to different levels (0.1, 1.0 and 10 μg/ml) of the toxin abrin have been isolated and characterized. The frequency of resistant colonies to abrin was increased with the concentration of a chemical mutagen. There was no effect of cell density or cross-feeding on the recovery of variants. In experiments using fluorescein-labeled abrin and ricin which bind to terminal (non-sialylated) galactose residues of cell-surface oligosaccharides, parental cells exhibited strong binding toward both toxins, whereas no fluorescence was observed in the resistant clones. A fluorescein-conjugated lectin, BS II, which is specific for terminal N-acetyl- -glucosaminyl residues, did not interact with the parental cells, but did with the resistant clones. This suggests that on the surface of resistant cells the number of terminal galactosyl residues of oligosaccharide chains in glycoproteins was reduced, exposing the penultimate N-acetyl- -glucosaminyl residues. The number of available endogenous acceptor sites for galactosyl transferase in the abrin-resistant clones was directly proportional to the degree of resistance. In the presence of great excess of exogenous acceptor, the rates of galactosyl transfer were similar in all the abrin-resistant cell types tested, with levels ranging from 1.4 to 1.7 times parental cell values. Studies with tetraploid cell hybrids reveal that resistance was a recessive trait. Fluctuation analysis showed that abrin resistance occurred in CHO cell populations at a rate of 4−7 × 10⁻⁸/cell/generation. The system may serve as a new marker for quantitative mutagenesis studies.