Some obstetrical aspects of the rapidly changing Wopkaimin society.
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Biomedical subjects
Publications and source records attributed to W Anderson.
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The personal characteristics of 80 clients with elevated 2-4 (D-PD) scales on their MMPIs were compared with those of 109 clients without these elevations. Clients with the 2-4 elevated were significantly more depressed, had lower self-esteem, and were more likely to come from disturbed families. They also had poor relationships with the opposite sex, became more dependent on the therapist, and often made little improvement in therapy. In comparison to previous descriptions of hospitalized patients with similar profiles, the counseling center clients continue to function in the community and show less pathological behavior. Implications for therapy are discussed.
Sera from 50 healthy old subjects and from 51 young controls were tested by ELISA assays for a panel of autoantibodies, including IgM RF, anti-DNA, anti-F(ab')2, antithyroglobulin, anti-human albumin, anti-human hemoglobin, anti-secretory component from human IgA, and anti-gliadin. In vitro production of anti-DNA as well as anti-F(ab')2 antibodies were measured after stimulation of PBMC by pokeweed mitogen (PWM) in 12 healthy elderly subjects and 11 young controls. Sera from elderly donors contained threefold higher amounts of IgM RF than young controls (P less than 0.001). On the contrary, the levels of anti-DNA as well as anti-F(ab')2 antibodies were similar in both groups (P less than 0.3 for the two determinations). Anti-DNA and anti-F(ab')2 antibodies were also measured in supernates of PWM-stimulated glass nonadherent PBMC cultures from both old and young healthy donors without finding any significant difference between the two groups. Additional ELISA tests were also performed in both elderly and young control sera to detect antibodies against six other different antigens. No significant difference was found in the percentages of positive sera between the two groups. This discrepancy in production of IgM RF compared to other autoantibodies in healthy elderly subjects does not provide support for a general increase of autoantibodies with aging. The biological significance of an increase in IgM RF with aging remains to be determined.
High-affinity monoclonal antibodies specific for the cardiac glycoside digoxin provide a useful system for the study of structure-function relationships between antibody combining site and specific antigenic determinants. Fifteen high-affinity monoclonal anti-digoxin antibodies were produced when spleen cells from A/J mice immunized with digoxin coupled to human serum albumin (Dig-HSA) were fused with the non-secreting murine myeloma Sp2/0 cell line. Each subcloned hybridoma antibody was analyzed for affinity and specificity for structurally related cardiac glycosides by a radioimmunoassay based on the adsorption of free [3H]digoxin to dextran-coated charcoal. All of the anti-digoxin hybridoma proteins demonstrated high affinity constants ranging from 10(9) to 10(12) M-1. Using seven different analogs of digoxin, binding specificities of the monoclonal antibodies were assessed by inhibition radioimmunoassay. The 15 hybridomas produced from fusions involving five mice could be divided into eight sets on the basis of these binding specificities. Certain antibodies exhibit a preference for the aglycone portion of digoxin, while others are more specific for the tridigitoxose sugar moiety of digoxin. Monoclonal antibody H- and L-chains were subjected to N-terminal amino acid sequence analysis. The antibodies may be divided into several sequence homology sets for both H- and L-chains. In most instances, homologous heavy chains are associated with a set of homologous light chains. Homologous partial sequences, however, do not correlate with similar antigenic specificities and affinities for digoxin. Thus the fine specificity for antigen is not dependent on VH- and VL-encoded sequences alone. These data illustrate the broad diversity of the elicited response to a single hapten, even in inbred mice.
Day 6 rabbit blastocysts that had previously been incubated with 10 nM [3H]prostaglandin E2 (PGE2), [3H] PGF2 alpha, or 0.5 microCi [3H]water were surgically transferred to the uteri of day 6 pseudopregnant recipient rabbits. At 1, 3, and 20 h after transfer, blastocysts were collected from the recipient rabbits and evaluated for retention of [3H]ligands. The transferred day 6 blastocysts were able to retain a significant proportion of the initial PGs for up to 20 h in vivo. These PGs were not metabolized while they remained in the blastocysts in vivo, as assessed by HPLC. The transferred blastocysts appeared normal and viable after 20 h in vivo, since implantation sites could be detected visually. These data support our hypothesis that blastocysts can sequester PGs from their environment in vivo and retain them unmetabolized during the critical period just before implantation.
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Maytansine, a potent inhibitor of mitosis and in vitro microtubule assembly, was used to demonstrate a striking difference in the mechanism by which two of the main groups of brain microtubule-associated proteins, Tau and MAP2, interact with tubulin. At the low concentrations of 0.5 to 2 microM, maytansine inhibited Tau-catalyzed tubulin assembly more effectively than it did MAP2-catalyzed assembly. This effect differed markedly from that of vinblastine, although both drugs bind competitively to tubulin. At the same low concentrations, vinblastine almost completely inhibited Tau- and MAP2-mediated tubulin assembly. At higher concentrations of 10 to 40 microM, a more striking difference was observed between the actions of the two drugs. Maytansine very effectively inhibited tubulin assembly promoted by either Tau or MAP2. Vinblastine also had this effect on MAP2-mediated tubulin assembly but in the presence of Tau induced extensive tubulin aggregation into spirals. In addition maytansine strongly inhibited vinblastine-induced Tau-dependent tubulin aggregation into spiral polymers. Even at very low concentrations, maytansine completely inhibited the effect of very high concentrations of vinblastine. These results very strongly suggest that the binding sites of maytansine and vinblastine on the tubulin molecule overlap and that the changes that they probably induce in the conformation of this molecule are markedly different, at least in the presence of microtubule-associated proteins.
The oedemagenic activities of several iota-carrageenans from Eucheuma spinosum have been compared using the rat hindpaw model. From the parent iota-carrageenan of weight average molecular weight 541 100 an acid-degraded iota-carrageenan (Mw = 20 300) was obtained which on fractionation yielded five iota-carrageenans Mw ranging from 73 700 to 4 600. The oedemagenic activity of iota-carrageenan resided in the fraction of Mw = 73 700, the parent undegraded high molecular weight iota-carrageenan being no more active and fractions of lower molecular weight being inactive. Fractionation was based on differential solubilities of the barium salts of the fractions in water and aqueous ethanol and was probably determined by aspects of primary structure in addition to molecular weight.
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Malaria and filariasis surveys were carried out as part of a broader general health survey between December, 1982 and May, 1983 in the Ok Tedi region of the Star Mountains, Western Province. Malaria, tropical splenomegaly syndrome (TSS) and anaemia were identified as significant health problems. Malaria slide positivity rates of 64.9% in children 2 to 9 years of age and 19.5% in adults 15 years and older indicate high levels of stable malaria transmission. Infections with Plasmodium falciparum were the most common (75.2%), but P. vivax (17.4%) and P. malariae (7.4%) were also encountered. Palpable splenomegaly occurred in 79.2% of adults and children over two years of age with more than 50% of the enlarged spleens grade III or greater (Hackett). Microfilariae (Wuchereria bancrofti) were present in 34.3% of night blood films, and estimated haemoglobin values were considerably below WHO standards. Data from the surveys provide a baseline against which to monitor changes in health status which might be expected to occur in conjunction with the development of a major mining project in the area.
Male Fischer 344 rats were fed ad libitum (Group A) or 60% of the ad libitum intake (Group R) starting at 6 weeks of age. The latter is a dietary manipulation that prolongs life. At 6, 10 and 15 weeks of age, rats were killed, free adipocytes prepared, and lipolytic, adenylate cyclase, and phosphodiesterase activities of adipocytes measured. The ability of glucagon to promote lipolysis markedly declined between 6 and 15 weeks of age in adipocytes from Group A rats but not in those from Group R rats. Glucagon-promoted adenylate cyclase activity paralleled lipolytic activity. Phosphosdiesterase activities increased with age, to a greater extent in adipocytes from Group A rats than in those from Group R rats. It is concluded that the loss in glucagon-promoted lipolysis with age in adipocytes from Group A rats is primarily the result of either a loss of or a change in the characteristics of the glucagon receptors or an alteration in the system coupling the receptors with adenylate cyclase and that food restriction prevents these changes. The relevance of these findings in analysis of the mode by which food restriction delays the aging process is discussed.
Changes with time in the anti-factor Xa activity of several heparins were determined in freshly autoclaved and unautoclaved dextrose solutions. In the former, activity was raised, in the latter a reversible fall occurred at certain heparin concentrations, and the term "dextrose effect' is applied to the difference in activity in the two types of dextrose solutions. A simple dependence on heparin concentration for the rise in activity in autoclaved dextrose solutions contrasted with a threshold heparin concentration in the unautoclaved dextrose solutions. Above this a fall and below it a rise in activity were demonstrated with one factor Xa method. The pH of the two dextrose solutions differed by one unit but pH was not the principal factor in the effect; salt tended to eliminate the dextrose effect which was found mostly with the high and to some extent also with the low molecular weight fractions of pharmacopoeial heparin. There was no evidence for heparin degradation but activity changes, which differed for different heparins, are thought to be associated with the effects of heparin-dextrose interaction modified in the case of autoclaved dextrose by by-products of autoclaving. Generally, proprietary dextrose solutions gave variable results.
The effect of dextrose on heparin was investigated using the heparin-azur A interaction as a measure of macroanionic activity. Dextrose solutions did not diminish heparin-azur A metachromasia but prior autoclaving of the dextrose solution resulted in a slight decrease. When calcium chloride was added to the dextrose (autoclaved or unautoclaved) there was a reduction which was greater than that caused by calcium ion in the absence of dextrose. The effects of calcium ion and dextrose acting together were each concentration - dependent. A low molecular weight fraction (8400) was more susceptible to the effects of calcium in the presence of dextrose than a fraction of mol. wt. 19 000, hence unfractionated heparins with different amounts of various fractions may respond differently to calcium in the presence of dextrose. This has not been considered in earlier studies of the anticoagulant activity of unfractionated heparins in dextrose infusion and could has contributed to reported discrepancies, particularly in view of the variety of test methods used. At present, it is not possible to predict from in vitro tests whether dextrose will modify the in vivo anticoagulant activity of heparin.
Gastric acid and pepsin secreted in 3 hr and antral gastrin released in response to vagal excitation induced by 2-deoxy-D-glucose (2DG), 625 mumol/kg i.v., were studied in six conscious trained gastric fistula dogs. During a 2-hr infusion, Met-enkephalin (96 nmol/kg/hr; delta receptor) reduced the 2DG response by 50%; when the enkephalin was stopped there was a rapid rebound to peak values. Met-enkephalin also blocked the release of gastrin in the first 15 min. By itself, Met-enkephalin did not stimulate secretion and slightly depressed gastrin. By contrast, morphine (96 nmol/kg/hr; mu receptor) augmented and sustained the 2DG gastric acid secretory response. This effect was blocked by naloxone. Morphine alone caused a small rise in serum gastrin after 90 min, followed by a delayed gastric acid secretion of about 30% of the peak 2DG response. Naloxone, a mu opiate antagonist (mu/delta, 27:1), also inhibited the 2DG gastric secretory response by about 50% and augmented the Met-enkephalin inhibition of secretion without blocking either the secretory rebound or the effect on gastrin release. None of the three opiates changed the direct cholinergic gastric secretory or gastrin-releasing effects of bethanechol. Thus, vagal stimulation of the stomach involves pathways which can be influenced by both mu and delta opiates, with apparently opposite effects, proximal to the level of acetylcholine action on the gastric mucosa. The central and peripheral control points in the activation of the stomach via the vagus which are sensitive to opiates have yet to be located and explained.
The conformational behavior of four tetrapeptide enkephalin analogues (Tyr-Gly-Gly-Phe-OH, Tyr-Gly-Gly-Phe-NH2, Tyr-D-Ala-Gly-Phe-NH2, and Tyr-D-Ala-Gly-(NMe)Phe-NH2) was examined to identify conformations that are active and inactive at the opiate analgesic receptor. By using an empirical energy program, conformational energies were obtained for the optimized geometries of each tetrapeptide. Two methods of selecting candidate active conformations from low-energy conformers were used. In the first method, inactive conformers were designated as low-energy conformations of the very weak tetrapeptide, Tyr-Gly-Gly-Phe-OH. These candidate inactive conformers had geometries resembling beta V, beta I, "random" peptide conformations. Candidate active conformers selected were low-energy conformations found for both Tyr-D-Ala-Gly-Phe-NH2 and Tyr-D-Ala-Gly-(NMe)Phe-NH2 but not low-energy conformers for Tyr-Gly-Gly-Phe-OH. In the second method of selection, conformers with relative energies in the active and inactive peptides that followed the potency order Tyr-Gly-Gly-Phe-OH much less than Tyr-D-Ala-Gly-Phe-NH2 less than or equal to Tyr-D-Ala-Gly-(NMe)Phe-NH2 were chosen as candidate active conformers. By using both methods of selection, a beta II' bend geometry was found as the active conformer. This beta II' conformer was not stabilized by a 1-4 hydrogen bond, but instead was stabilized by a hydrogen bond between the tyrosine amine hydrogen atom and the phenylalanine carbonyl oxygen atom. The effect of C-terminal amide derivitization on peptide conformation was also examined by comparing the conformational profiles of Tyr-Gly-Gly-Phe-OH and Tyr-D-Ala-Gly-Phe-OH with their amides Tyr-Gly-Gly-Phe-OH-NH2 and Tyr-D-Ala-Gly-Phe-NH2. No significant difference in conformational behavior was found for the Tyr-Gly-Gly-Phe pair; however, a difference in conformational behavior was found between the Tyr-D-Ala-Gly-Phe acid and amide. Thus, on the basis of conformational data, the Tyr-Gly-Gly-Phe-NH2 analogue is predicted to have very weak opiate activity.
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