MPD and DNA bending in crystals and in solution

Bending of 15 to 24 degrees is observed within crystal structures of B-DNA duplexes, is strongly sequence-dependent, and exhibits no correlation with the concentration of MPD (2-methyl-2,4-pentanediol) in the crystallizing solution. Two types of bends are observed: facultative bends or flexible hinges at junctions between regions of G.C and A.T base-pairs, and a persistent and almost obligatory bend at the center of the sequence R-G-C-Y. Only A-tracts are characteristically straight and unbent in every crystal structure examined to date. A detailed examination of normal vector plots for individual strands of a double helix provides an explanation, in terms of the stacking properties of guanine and adenine bases. The effect of high MPD concentrations, in both solution and crystal, is to decrease local bending somewhat without removing it altogether. MPD gel retardation experiments provide no basis for choosing among the three models that seek to explain macroscopic curvature of DNA by means of microscopic bending: junction being, bent A-tracts, or bent general -sequence DNA. Crystallographic data on the straightness of A-tracts, the bendability of non-A sequences, and the identity of inclination angles in A-tract and non-A-tracts B-DNA support only the general-sequence bending model. The pre-melting transition observed in A-tract DNA probably represents a relaxation of stiff adenine stacks to a flexible conformation more typical of general-sequence DNA.     

Research and teaching in social and preventive medicine and in public health

Both public health and social and preventive medicine are characterised by the common goal of promoting, maintaining and improving health and preventing disease, and both are concerned with a population-related, preventive and environmental perspective. But whereas public health is interdisciplinary and goes far beyond the medical focus, social and preventive medicine is medically based and forms a bridge between public health and medical practice. Research in a department of social and preventive medicine serves to support preventive and medico-social activities in medical practice as well as in public health. This is illustrated by results from research conducted at the author's department during the last twenty years. Examples are research in support of smoking cessation activities, and research used for the planning of care for the elderly. Both the research and the teaching activities of the department take into account the population focus of public health as well as the focus on individual medicine in clinical practice.     

Identification and changes in prejudice and in authoritarianism.

Ss "were first given the F Scale and a measure of anti-Negro prejudice… . Four weeks later they read a case history of a person who was prejudiced and authoritarian. Half of the subjects were told that the person in the case history was similar to themselves in background and objective personal characteristics. The other half… that the person was dissimilar to them. Three weeks later the F Scale and the anti-Negro prejudice scale were readministered. It was found that those low in prejudice at the first administration became more prejudiced but only if they were told the case history was about someone like themselves… . These results were interpreted in terms of the social support for suppressed 'wrong' feelings and in terms of the pressures to achieve cognitive consistency in one's self-concept." From Psyc Abstracts 36:04:4GD65S. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemo- and baroresponses differ in African-Americans and Caucasians in sleep

To determine sleep effects on baro- and ventilatory responses to transient chemo- and barostimulation in African-Americans and Caucasians, 26 nonobese normotensive young subjects (13 African-Americans and 13 Caucasians) were studied awake and in non-rapid-eye movement (NREM) and rapid-eye-movement sleep during induced transient hypoxemia (N2), hypertension (phenylephrine, PE), and concomitant hypoxemia and hypertension (N2 + PE). Arterial blood pressure was recorded by plethysmographic volume clamp, minute ventilation by pneumotachograph, and arterial O2 saturation by pulse oximeter. For all subjects, chronotropic baroresponse (Deltapulse interval/Deltasystolic blood pressure, where Delta is change) increased with NREM sleep (P = 0.007). Baroresponse slope was greater in Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatory response (Deltaminute ventilation/Deltaarterial O2 saturation) was greater in African-Americans than in Caucasians in NREM sleep (P = 0.01), as was hypoxemic attenuation of baroresponse (N2 + PE, P = 0.03). These data suggest sleep-related differences in arterial chemo- and baroreceptor responses in normal young African-Americans and Caucasians, which may have implications concerning development of systemic hypertension.     

Protein phosphorylation and taurine biosynthesis in vivo and in vitro

Taurine is known to be involved in many important physiological functions. Here we report that both in vivo and in vitro the taurine-synthesizing enzyme in the brain, namely cysteine sulfinic acid decarboxylase (CSAD), is activated when phosphorylated and inhibited when dephosphorylated. Furthermore, protein kinase C and protein phosphatase 2C have been identified as the enzymes responsible for phosphorylation and dephosphorylation of CSAD, respectively. In addition, the effect of neuronal depolarization on CSAD activity and 32P incorporation into CSAD in neuronal cultures is also included. A model to link neuronal excitation and CSAD activation by a Ca2+-dependent protein kinase is proposed.     

Differences and similarities in adjuvant chemotherapy in mouse and man

Supernatants obtained after incubation of tumor patient lymphocytes with the homologous tumor-associated antigen (TAA) elicit adherence inhibition in normal guinea pig peritoneal cells. From 37 tested patients with different carcinomas, the supernatants of 30 caused more than 10 per cent adherence inhibition (breast cancer 11/11, lung cancer 7/8, colon cancer 6/7, stomach cancer 6/11). Besides 40 healthy blood donors were tested to a panel of TAA. There was a reactivity more than 10 per cent only in 2 cases. The supernatants of 14 patients with nonmalignant disorders produced adherence inhibition more than 10 per cent in 2 cases. By incubation of tumor patient lymphocytes with the human encephalitogenic protein the supernatants of 19/27 patients elicited a positive reaction. The results suggest that anti-tumor immunity can be detected in an indirect heterologous adherence inhibition system.     

Cholestatriene and ergostatetraene as in vivo and in vitro membrane and lipoprotein probes

The fluorescent cholesterol analogues, cholesta-5,7,9(11)triene-3-beta-ol (I) and ergosta-5,7,9(11)-22-tetraene-3-beta-ol (II), have been shown to be readily incorporated by various tissues and lipoproteins in rabbits maintained on diets supplemented with these fluorophores. Human erythrocytes and lipoproteins were also found to incorporate I and II in vitro under physiological conditions. The thermotropic behavior of the lipoproteins and erythrocyte membranes labeled with sterols I and II was evaluated using temperature-dependent fluorescence polarization and/or fluorescence intensity spectra. Erythrocyte ghosts, fluorescently labeled in vivo (rabbit) or in vitro (rabbit and human), were found to undergo a reversible thermally induced transition at 24 +/- 2 degrees C. A similar transition occurring at higher temperatures was also observed in fluorescently labeled human and rabbit LDL particles. Furthermore, the transition temperatures and relative microviscosities of the in vivo labeled rabbit LDL particles were found to be dependent upon the amount of sterol present in the rabbits' diet. No evidence of a similar thermotropic transition was observed in any of the HDL particles. These results are discussed in terms of a thermotropic reordering of cholesterol clusters existing in the erythrocyte membrane and of the cholesteryl ester core present within the low density lipoprotein particle.     

Platinum concentrations in urban road dust and soil, and in blood and urine in the United Kingdom

Increasing Pt concentrations from vehicle catalysts have been reported from a number of countries. Analysis of Pt and Pd in soils and road dusts taken from areas of high and low traffic flows in SE England show concentrations of Pt in the range < 0.30-40.1 ng g-1 and Pd in the range < 2.1-57.9 ng g-1. Higher concentrations of Pt are associated with high traffic densities. Samples taken from streets of lower traffic flows were found to contain the lower concentrations of the ranges. Pilot studies of Pt concentrations in blood and urine using ICP-MS have been carried out. Platinum concentrations in whole blood were: precious metal workers, 780-2170, mean 1263 pmol l-1 (0.152-0.423, mean 0.246 microgram l-1); motorway maintenance workers, 645-810, mean 744 pmol l-1 (0.126-0.158, mean 0.145 microgram l-1); Imperial College staff, 590-713, mean 660 pmol l-1 (0.115-0.139, mean 0.129 microgram l-1). Platinum concentrations in urine in pmol Pt per mmol creatinine were: precious metal workers, 122-682, mean 273 [0.21-1.18, mean 0.47 microgram Pt (g creatinine)-1]; motorway maintenance workers, 13-78, mean 33.7 [0.022-0.135, mean 0.058 microgram Pt (g creatinine)-1]; Imperial College staff, 28-130, mean 65.6 [0.048-0.224, mean 0.113 microgram Pt (g creatinine)-1]. Detection limits were 0.03 microgram l-1 for both blood and urine. The possible health effects of increasing Pt in the environment are discussed. Platinum provides an excellent example of the significance of speciation in metal toxicity. Platinum allergy is confined to a small group of charged compounds that contain reactive ligand systems, the most effective of which are chloride ligand systems. Metallic Pt is considered to be biologically inert and non allergenic and since the emitted Pt is probably in the metallic or oxide form, the sensitising potential is probably very low. Platinum from road dusts, however, can be solubilised, and enter waters, sediments, soils and the food chain. There is at present no evidence for any adverse health effects from Pt in the general environment, particularly allergic reactions.     

Photoreactivation in bacteria and in skin

In many procaryotic and eucaryotic cells, photoreactivating enzyme mediates light-dependent repair of UV-induced damage: the enzyme binds to a pyrimidine dimer in DNA, and, on absorption of a photon (300-600 nm), specifically monomerizes the dimer, thus repairing the DNA. Photoreactivating enzyme has been found in human tissues and human cells in culture; human cells in culture can photoreactivate cellular dimers, and can mediate photoreactivation of Herpes (human fibroblasts) and Epstein-Barr virus (human leukocytes). Measurements of pyrimidine dimer formation and repair in human skin indicate that detectable numbers of dimers are formed at 1 minimal erythemal dose, that the dimers are rapidly removed in skin kept in the absence of light, and they are more rapidly removed when the skin is exposed to visible light.     

Comparative binding and toxicity of saxitoxin and saxitoxinol in mice and in cultured cells

The binding characteristics of saxitoxin (STX), a known voltage-gated sodium channel blocker, and its analog saxitoxinol (STXOL), were studied in neuroblastoma, peritoneal macrophage, hepatocytes and PC-12 cell lines. 3H-STXOL bound to the cell-surface sites which appear to be the same as those occupied by 3H-STX and which can, therefore, be identified as STX receptors. The relative agreement of respective Kd obtained by saturation, competition, association and dissociation kinetics for STX and STXOL suggest the absence of any artifact in binding measurements. Unlike STX, STXOL was non-toxic to mice by intratracheal instillation. The major advantage of using 3H-STXOL is that the tritium label is not exchangeable. Data from this study suggest that 3H-STXOL can be used to identify STX receptors at 37 degrees C.     

Stability and change in aggression and withdrawal in middle childhood and early adolescence.

Examined stability and change in aggression and withdrawal in the context of both normal and deviant behavioral development. The design included 3 age cohorts with a total of 653 Ss separated in age by 3 yrs. Aggression and withdrawal were measured using the Peer Evaluation Inventory initially when the Ss were in Grades 1, 4, and 7 and a 2nd time when the Ss were in Grades 4, 7, and 10, respectively. Members of 4 classification groups were included in the sample: 183 Ss in an aggressive group, 219 Ss in a withdrawn group, 251 Ss in an aggressive-withdrawn group, and a nondeviant control group consisting of 1,103 Ss. The stability of aggression was found to be moderately high, regardless of sex of S or grade at time of initial assessment. Moderate stability was found for withdrawal for both boys and girls when initial assessments were conducted at Grades 4 and 7. The withdrawn Ss became more withdrawn over the 3-yr period. It is concluded that, for many children, the problems of aggression and withdrawal do not appear to be transitory. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations in metabolism of H-epinephrine in the pregnant and non-pregnant state and in males

The influence of sex, pregnancy and parturition of biological accumulation and metabolic fate was studied in Sherman rats. 3H-epinephrine was used as a tracer to determine differences in metabolite formation in normal males and females as well as pregnant rats from 18 days post coitum to the end of parturition. The disappearance of 3H-epinephrine and its metabolites was measured in blood, heart, kidney and brain at different intervals but 20 min after the injection of tracer was found the most appropriate time to find appreciable radioactivity in most of the organs studied. All the comparisons for 3H-epinephrine accumulation and its transformation to metabolites have been reported 20 min post-perfusion period. Marked changes of high statistical significance in 3H-epinephrine accumulation and its transformation to 3H-metanephrine and 3H-acid metabolities were observed between males and females. Heart, adrenals, and spleen showed lower rate of metabolism but higher rate of accumulation during pregnancy. Kidney, ovary, and uterus demonstrated higher rate of metabolism but lower rate of accumulation during gestation. In brain regions, hypophysis discriminated greatly between males and females for the three parameters studied. There were important alterations in metabolite formation during 18 and 21 days of pregnancy. The observed variations have been considered due to modified endocrine activity during pregnancy and parturition.     

Pretectum and superior colliculus in visually guided behavior and in flux and form discrimination in the cat.

Monocularly trained 11 adult split-brain cats with unilateral ablation of pretectum and/or superior colliculus in flux and form discriminations. When the midbrain lesions involved both colliculus and pretectum, there was a severe impairment in learning pattern discriminations using the eye on the lesion side. In those cases with the lesions chiefly in the colliculus or in pretectum, the deficit was present but less marked. When these same discriminations were taught before the midbrain lesion, no loss in retention was found postoperatively. (78 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Changes in steroid hormones in plasma and myometrium and uterine activity in ewes during late pregnancy and parturition

In 7 ewes during late pregnancy, peripheral plasma concentrations of oestrogens were correlated with uterine activity (P less than 0-01; r=+0-47). In myometrial tissue, the concentration of progesterone was similar to that in plasma; it rose to a plateau from Days 115 to 130 of pregnancy and then fell, but was still detectable during parturition. Myometrial oestrogen concentration was much higher than in plasma; from a peak at Days 100-115 it decreased, but rose sharply just before parturition.     

Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood

Placental transfer and metabolism of carbamazepine (CBZ) was studied in a dual recirculating placental cotyledon perfusion system and was also evaluated in 16 pairs of maternal venous and cord blood samples. Among the parameters studied as possible indicators of a successful perfusion, volume changes in perfusate divided the perfusions into two groups, whereas no significant differences between perfusions were noted in blood gas analysis or in antipyrine transfer. CBZ added into the maternal circulation crosses the placenta in the beginning quicker than antipyrine which is in agreement with the different lipid solubilities of these compounds. Because the transfer rates of antipyrine and CBZ were about the same, the mechanism of transfer of CBZ is probably similar to that of antipyrine (passive diffusion). No metabolites of CBZ could be detected in the perfusate by high-performance liquid chromatography (HPLC) or gas chromatography/mass spectrometry. With the improved HPLC methodology for CBZ metabolites, six metabolites were detected in clinical samples, including 10-hydroxy-10,11-dihydro-CBZ (10-OH-CBZ), which has been described earlier in only 1 uremic patient. Relative levels of metabolites showed significant individual differences. CBZ crosses perfused placenta rapidly, but this does not contribute to CBZ metabolites detected in maternal and fetal circulation.     

Development and maintenance of bile canaliculi in vitro and in vivo

Four types of high-flux hemodialyzers, Primus 2000 (high-flux polysulfone 2.0 m2), Altra-Flux 170 G (cellulose diacetate 1.7 m2), FLX-15 GW (polyester-polymer alloy 1.5 m2) and PAN-85 DX (polyacrylonitrile 1.7 m2) were evaluated in vivo. A total of 12 stable chronic hemodialysis patients participated in the study and each type of dialyzer was tested once in 9 of them. Blood samples for the measurement of BUN, creatinine, phosphate, uric acid, albumin and beta2-microglobulin (beta2M) were drawn before and 5 min after the end of the study dialysis. During dialysis, which was performed in all patients with a blood flow rate of 250 ml/min for 240 min, the dialysate (550-600 ml/min) was collected every hour and samples were drawn for the measurements of all the above substances. The mean total amount of low-molecular substances removed per session by each dialyzer was very close to 19.5 g for urea, 2.0 g for creatinine, 0.9 g for phosphate and 1 g for uric acid. The one-third (30-33%) of the above amounts were removed during the first hour of dialysis. Dialyzers' clearances for creatinine and uric acid were significantly higher in Primus dialyzer comparing to FLX-15 GW (p < 0.05) while the clearance for urea showed a borderline significance (p = 0.055). No difference was found either among Altra-Flux 170 G, FLX-15 GW and PAN-85 DX or between Primus and PAN-85 DX dialyzers. Phosphate clearance did not show any difference among the four dialyzers. The lowest amount of albumin removed per session was 0.75 g by PAN-85 DX and the highest 1.8 g by FLX-15 GW, while the equivalents for beta2M were 80 mg by Altra-Flux 170 G and 142 mg by PAN-85 DX. A significant adsorption of beta2M on these dialysis membranes was indicated by the combination of a satisfactory serum beta2M reduction ratio (post-/predialysis values = 0.52, 0.77, 0.60, 0.55) with a reduced beta2M clearance (23.9, 13.6, 20.2, 25.1 ml/min). During the first hour of dialysis, in comparison to the following time, the highest amounts of albumin and beta2M (expressed as percentage of total) were removed by the Primus 2000 dialyzer. Our results indicate that under conventional conditions small differences in the surface area of the high-flux dialyzers are unimportant regarding the removal of low molecules. However, the composition of the membrane seems to play an important role in the removal of high-molecular substances.     

Caregiving and infant behavior in day care and in homes.

Social interaction and play behavior were compared in community-based day care and at home for 2 matched groups of 18-mo-olds (30 Ss). Adult–infant, infant–peer, and infant–toy interaction were time sampled. More adult–infant play, tactile contact, and reciprocal smiling were found in day care. More infant verbal responsiveness to maternal talking, more infant crying, and more maternal restrictiveness were found at home. Developmental level of play with toys was higher in day care, a difference associated with interaction with peers. The importance of the infant in shaping the environment emerged clearly from the data; day care/home differences in adult–infant interaction were often a function of differences in infant as well as adult behavior. No adverse effects of daily mother–infant separation were noted in the daily social and play behavior of the day-care group. The importance of peers as social objects for the toddler emerged from this study. Peers seemed to contribute to the high levels of play and to the positive affect noted in day care and also seemed to facilitate separation from adult caregivers. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lead and cadmium contents in cereals and pulses in north-eastern China

A mechanistic model is proposed for describing the accumulation of copper in Hyalella azteca. The metal is assumed to diffuse passively into and out of the animal. Once inside, it binds primarily to a ligand (X), the function of which is probably to supply copper to copper-requiring essential macromolecules. Once X is saturated, no further copper is accumulated. The rate of approach to the steady-state is much faster during uptake than during depuration because the number of binding sites (Xt) is limited. Diffusion across the animal's body surface does not seem to be rate-limiting. The binding strength of copper to X (KCu-X) is stronger than the binding of copper to fish gills, but this is not necessarily a valid comparison because KCu-X is the product of several constants, including the equilibrium for diffusion across the animal's surface and the strength of the internal binding site. Prolonged exposure to elevated copper in the water gradually reduces the concentration of Xt, primarily through growth dilution. Regulation of body copper appears to be through control of the concentration of Xt, rather than through control of copper influx or efflux rates, and chronic mortality is not affected by changes in Xt.     

Coagulation and fibrinolysis parameters in normal pregnancy and in gestational diabetes

The changes in coagulation and fibrinolysis parameters during pregnancy, delivery and 3 days after delivery were evaluated in normotensive and gestational diabetes pregnant women. Normal pregnant women (n = 60) and pregnant women with gestational diabetes (n = 15) formed the study population. Coagulation and fibrinolysis parameters were estimated using commercial tests. Antithrombin III, thrombin-antithrombin III complexes, heparin cofactor II, protein C, protein S, tissue plasminogen activator, (t-PA) D-dimer and plasminogen activator inhibitor (PAI-1 and PAI-2) activities in normal and gestational diabetes pregnancies were determined. Thrombin-antithrombin III complexes increased and coagulation inhibitors decreased in gestational diabetes. Plasminogen activator inhibitors remained unchanged and t-PA levels increased in gestational diabetes.     

Attraction and repulsion by life and death in suicidal and in normal children.

Attraction and repulsion by life and death in 52 suicidal and 58 normal 6–12 yr olds were measured through responses to questions that followed fairy-tale stories. Each story represented 1 of the 4 attitudes. Parallel forms of the test were administered in a time interval of 4 wks. Analyses showed that the 4 attitudes were distinguishable from each other and that the response profile of the suicidal Ss was significantly different from that of normal Ss. Suicidal Ss, in contrast to normal Ss, showed a high degree of repulsion by life and attraction to death and a low degree of attraction to life and repulsion by death. In addition, in suicidal Ss the 4 attitudes were more distinguishable from each other but at the same time were more conflictual. The correlations between the scores of the 1st administrations indicate that 3 of the 4 attitudes have a moderate reliability for both normal and suicidal children. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)