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Biomedical subjects

J Lydon

Publications and source records attributed to J Lydon.

At least 19 recordsLinked to original sources

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Adult↗

Detection of tabtoxin-producing strains of Pseudomonas syringae by PCR.

AIMS: The present study describes a system based on PCR to distinguish tabtoxin-producing strains of Pseudomonas syringae from other Ps. syringae plant pathogens that produce chlorosis-inducing phytotoxins. METHODS AND RESULTS: Thirty-two strains of Ps. syringae and related species were examined. Two sets of PCR primers were developed to amplify genes (tblA and tabA) required for tabtoxin production. Only a PCR product of 829 bp or 1020 bp was produced in PCR reactions with the tblA or tabA primer sets, respectively, and cells from tabtoxin-producing pathovars of Pseudomonas syringae. All known non-tabtoxin producing bacterial species failed to produce an amplification product with either primer set. CONCLUSIONS: PCR of genes required for tabtoxin production is a simple, rapid and reliable method for identifying tabtoxin-producing strains of Ps. syringae. SIGNIFICANCE AND IMPACT OF THE STUDY: The protocol can effectively distinguish tabtoxin-producing strains of Ps. syringae from other Ps. syringae pathovars and Ps. syringae pv. tabaci strains from other tabtoxin-producing Ps. syringae pathovars.

Dipeptides↗

Socio-economic disparities in pregnancy outcome: why do the poor fare so poorly?

In this paper, we review the evidence bearing on socio-economic disparities in pregnancy outcome, focusing on aetiological factors mediating the disparities in intrauterine growth restriction (IUGR) and preterm birth. We first summarise what is known about the attributable determinants of IUGR and preterm birth, emphasising their quantitative contributions (aetiological fractions) from a public health perspective. We then review studies relating these determinants to socio-economic status and, combined with the evidence about their aetiological fractions, reach some tentative conclusions about their roles as mediators of the socio-economic disparities. Cigarette smoking during pregnancy appears to be the most important mediating factor for IUGR, with low gestational weight gain and short stature also playing substantial roles. For preterm birth, socio-economic gradients in bacterial vaginosis and cigarette smoking appear to explain some of the socio-economic disparities; psychosocial factors may prove even more important, but their aetiological links with preterm birth require further clarification. Research that identifies and quantifies the causal pathways and mechanisms whereby social disadvantage leads to higher risks of IUGR and preterm birth may eventually help to reduce current disparities and improve pregnancy outcome across the entire socio-economic spectrum.

Canada↗

Realignment of a smectic-A phase with applied electric field

The realignment of a smectic-A phase contained in a conventional display device (with a mesophase layer approximately 10 &mgr;m thick) in response to an applied electric field has been studied using polarizing microscopy and x-ray diffraction. The initial state of the mesophase was a highly aligned focal conic texture. The applied field created a striated texture with parallel (but not equally spaced) disclination lines which appeared to be created in pairs. The lines seem to grow from disclination "eyes" in the original texture, linking them first in pairs, and then in long chains, as the field is increased. We suggest that the center of each pair of striations corresponds to a disclination wall and that the texture consists of a parallel array of smectic layers arranged in concentric flattened half-cylinders. Previous electro-optic studies of cells of this type have described the striated, field-on texture but appear to have overlooked the role of the defects in the original texture as growth points for the striations. However, there are structural similarities with two related studies where the field-induced disturbance of the mesophase starts with the production of toroidal focal conics-similar to those we propose.

Journal Article↗

Isolation and expression of PASK, a serine/threonine kinase, during rat embryonic development, with special emphasis on the pancreas.

We report the isolation and characterization of a serine/threonine kinase expressed during rat pancreas development. This kinase was cloned as part of a general screen using degenerate oligonucleotides to map expression of kinases and receptors during the course of pancreatic development. Sequence analysis showed it to be a member of the ste20-like serine/threonine kinase family. Northern blotting analysis against both fetal and adult tissues showed two transcripts, one of 2 kb and the other of 4 kb. The ratio of transcript expression varied with the tissue. In situ hybridization analysis showed that this gene is expressed in the early gut and pancreatic epithelium. By embryonic Day 15, the transcript is localized to cells that will eventually become exocrine in nature. In situ hybridization analysis also demonstrated high levels of expression in the choroid plexus, the developing myocardium, kidney, CNS, dorsal root ganglia, and testes. In addition, a search of the EST database revealed a related human kinase not previously described.

Amino Acid Sequence↗

Priming relational schemas: effects of contextually activated and chronically accessible interpersonal expectations on responses to a stressful event.

The authors used a relational schemas approach to test the effects of interpersonal expectations on responses to a stressful event. In Study 1, a subliminal priming technique was used to demonstrate the causal influence of experimentally activated interpersonal expectations on affect, support seeking, and coping responses to a hypothetical unplanned pregnancy. Activation of positive interpersonal expectations increased reports of seeking emotional support and decreased the use of self-denigrating coping. Activation of negative interpersonal expectations decreased reports of positive affect and tended to impede growth-oriented coping. Chronically accessible interpersonal expectations, assessed by an attachment questionnaire, were also associated with affect, seeking of support, and coping. Study 2 undermined the possibility that the experimental findings obtained with this priming procedure resulted from a mood manipulation.

Adaptation, Psychological↗

Herbicide residues in leaves of Erythroxylum coca var. coca plants treated with soil-applied tebuthiuron and hexazinone.

The herbicide residue levels in leaves of Erythroxylum coca var. coca Lam. plants treated with soil applications of tebuthiuron and hexazinone at 3.36 and 6.72 kg a.i. ha-1 were determined in order to estimate the potential for human exposure to these residues from consuming the leaves or cocaine produced from them. Field-grown plants were treated with a commercial formulation of tebuthiuron or hexazinone and leaves were harvested at the first indication of herbicide injury (i.e. chlorosis and/or necrosis) and at the onset of leaf abscission. Herbicide residues were detected by HPLC in leaf samples from both harvests of all plants treated with tebuthiuron or hexazinone. At 3.36 kg ha-1, herbicide residues in the leaves were less than 2 micrograms g-1 dry wt. for both harvests of both experiments. The highest residue levels detected were 5.90 micrograms g-1 dry wt. for tebuthiuron and 7.17 micrograms g-1 dry wt. for hexazinone in leaves from plants treated with the herbicide at the rate of 6.72 kg ha-1 and harvested at the onset of leaf drop. Based on published toxicity data and estimates of leaf consumption, the herbicide residues in leaves of E. coca var. coca plants treated with tebuthiuron or hexazinone at twice the recommended control rates or less would have a negligible contribution to the health risks of individuals who chew coca leaves. Furthermore, based on the most conservative estimates of cocaine yield and herbicide carry over, death by cocaine overdose would occur long before the NOEL for either herbicide was reached.

Cacao↗

Effects of components of Artemisia annua on coccidia infections in chickens.

Four experiments were run to test the anticoccidial activity of dried Artemisia annua leaves and several of their chemical constituents for possible use as prophylactic feed additives. When fed over a period of 3 wk at a level of 5%, a dried leaf supplement of A. annua provided significant protection against lesions due to Eimeria tenella but not Eimeria acervulina or Eimeria maxima. When fed over a period of 5 wk at a level of 1% to chicks undergoing immunization with a live vaccine, it provided significant protection in partially immunized chicks against E. acervulina and E. tenella lesions from a dual species challenge infection. It also afforded lower mean lesion scores in challenged chicks immunized over a period of 5 wk. Artemisinin, an antimalarial component of A. annua, was present at a level of 0.034% in the dried leaf preparation. A 5% supplement thus afforded about 17 ppm artemisin. When the pure compound was fed at that level for a period of 3 wk, it protected weight gains and significantly reduced lesion scores attributable to E. tenella but not E. acervulina. Other components of A. annua, camphor and 1,8-cineole, at 119 ppm also protected weight gains, and reduced E. tenella lesion scores. Camphor reduced E. acervulina lesions. Artemisinin fed for 4 wk at levels of 2, 8.5, and 17 ppm significantly reduced oocyst output from separate E. acervulina and E. tenella infections and a dual species infection. Pure artemisinin thus appears to be effective against at least two coccidia species when used as a feed additive, and its activity may depend, in part, on the length of time it is administered before a challenge infection.

Analysis of Variance↗

Mammary gland development is mediated by both stromal and epithelial progesterone receptors.

A combination of a knockout mouse model, tissue transplantation, and gene expression analysis has been used to investigate the role of steroid hormones in mammary gland development. Mouse mammary gland development was examined in progesterone receptor knockout (PRKO) mice using reciprocal transplantation experiments to investigate the effects of the stromal and epithelial PRs on ductal and lobuloalveolar development. The absence of PR in transplanted donor epithelium, but not in recipient stroma, prevented normal lobuloalveolar development in response to estrogen (E) and progesterone (P) treatment. Conversely, the presence of PR in the transplanted donor epithelium, but not in the recipient stroma, revealed that PR in the stroma may be necessary for ductal development. Members of the Wnt growth factor family, Wnt-2 and Wnt-5B, were employed as molecular markers of steroid hormone action in the mammary gland stroma and epithelium, respectively, to investigate the systemic effects of E and P. Hormonal treatment of intact, ovariectomized, and PR-/- mice and mice after transplantation of PR-/- epithelium into wild type (PR+/+) stroma demonstrated that these two locally acting growth factors are regulated by independent mechanisms. Wnt-2 is acutely repressed by E alone, while Wnt-5B gene expression is induced only after chronic treatment with both E and P. Wnt 5B appears to be one of the few molecular markers of P action in the mammary epithelium. This study suggests that the regulation of mammary gland development by steroid hormones is mediated by distinct effects of the stromal and epithelial PR and differential growth factor expression.

Animals↗

Renal epithelial protein (Apx) is an actin cytoskeleton-regulated Na+ channel.

Apx, the amphibian protein associated with renal amiloride-sensitive Na+ channel activity and with properties consistent with the pore-forming 150-kDa subunit of an epithelial Na+ channel complex initially purified by Benos et al. (Benos, D. J., Saccomani, G., and Sariban-Sohraby, S.(1987) J. Biol. Chem. 262, 10613-10618), has previously failed to generate amiloride-sensitive Na+ currents (Staub, O., Verrey, F., Kleyman, T. R., Benos, D. J., Rossier, B. C., and Kraehenbuhl, J.-P.(1992) J. Cell Biol. 119, 1497-1506). Renal epithelial Na+ channel activity is tonically inhibited by endogenous actin filaments (Cantiello, H. F., Stow, J., Prat, A. G., and Ausiello, D. A.(1991) Am. J. Physiol. 261, C882-C888). Thus, Apx was expressed and its function examined in human melanoma cells with a defective actin-based cytoskeleton. Apx-transfection was associated with a 60-900% increase in amiloride-sensitive (Ki = 3 microM) Na+ currents. Single channel Na+ currents had a similar functional fingerprint to the vasopressin-sensitive, and actin-regulated epithelial Na+ channel of A6 cells, including a 6-7 pS single channel conductance and a perm-selectivity of Na+:K+ of 4:1. Na+ channel activity was either spontaneous, or induced by addition of actin or protein kinase A plus ATP to the bathing solution of excised inside-out patches. Therefore, Apx may be responsible for the ionic conductance involved in the vasopressin-activated Na+ reabsorption in the amphibian kidney.

Actins↗

Antigen retrieval in cryostat tissue sections and cultured cells by treatment with sodium dodecyl sulfate (SDS).

A simple method for antigen retrieval in tissue sections and cell cultures is described. Because many antibodies recognize denatured proteins on western blots, but are poorly reactive by immunocytochemistry, the effect of applying sodium dodecyl sulfate (SDS) to cryostat sections of tissues and to cell cultures prior to immunostaining was examined. In many cases, a 5-min pretreatment with 1% SDS produced a dramatic increase in staining intensity by indirect immunofluorescence. Among the antibodies tested that showed a positive effect of SDS were an anti-Na/K-ATPase monoclonal antibody, an anti-AE1/2 anion exchanger polyclonal antipeptide antibody, a monoclonal anti-caveolin antibody, and an anti-rab4 monoclonal antibody. In other cases, including antibodies against gp330, aquaporin 1, and aquaporin 2, no effect of SDS was detected. The results show that SDS treatment can be used as a simple method of antigen retrieval in cryostat sections and on cultured cells. In some cases, antigens were not detectable without pretreatment with SDS.

Animals↗

Pregnancy decision making as a significant life event: a commitment approach.

A value-laden basis for commitment to goals and the behavioral and affective sequelae of commitment were examined in the context of a stressful life event. Fifty-seven women who were interviewed during a clinic visit for a pregnancy test (Time 1 [T1]) subsequently received positive test results and were then interviewed 2 days later (Time 2 [T2]) and a month later (Time 3 [T3]). The intentionality and the meaning of the pregnancy were associated with self-reported commitment to the pregnancy at T1. In turn, commitment predicted affective states both prior to (T1) and shortly after (T2) receiving test results. Initial commitment also predicted decisions to continue versus to terminate the pregnancy. The decision to continue the pregnancy appeared to bolster self-reported commitment. Relatedly, those continuing the pregnancy reported smoking fewer cigarettes at T3 than at T1. For those aborting the pregnancy, commitment at T1 was negatively related to adjustment at T3. Initial commitment predicted subsequent depression, guilt, hostility among those who aborted, whereas commitment predicted anxiety among those who continued the pregnancy. Other correlates of commitment (pregnancy concerns, religion, abortion history, and other life goals) were explored.

Abortion Applicants↗

Determination and in-depth chromatographic analyses of alkaloids in South American and greenhouse-cultivated coca leaves.

Methodology is described for the detection and/or determination of cocaine and minor alkaloids in South American coca as well as in greenhouse- and tropical-cultivated field coca of known taxonomy. Coca leaf from Bolivia, Peru, Ecuador and Colombia were subjected to the determination of cocaine, cis- and trans-cinnamoylcocaine, tropacocaine, hygrine, cuscohygrine and the isomeric truxillines. The greenhouse samples were cocaine-bearing leaves of the genus Erythroxylum and included E. coca var. coca, E. novogranatense var. novogranatense and E. novogranatense var. truxillense, and the alkaloids determined were cocaine, ecgonine methyl ester, cuscohygrine, tropacocaine and the cinnamoylcocaines. The tropical-cultivated coca were E. novogranatense var. novogranatense and E. coca var. coca. Cocaine and minor alkaloids were isolated from basified powdered leaf samples using a toluene extractant, followed by acid-Celite column chromatography. The isolated alkaloids were determined by capillary gas chromatography with flame ionization or electron-capture detection. Methodology is also presented for the isolation and mass spectral analysis of numerous trace-level coca alkaloids of unknown structure.

Alkaloids↗

Treatment of medulloblastoma in adults.

Seventeen adult patients with medulloblastoma were treated at Rush-Presbyterian-St. Luke's Medical Center and affiliated hospital between 1969 and 1986. All patients had a surgical procedure (total excision in seven patients, partial resection in nine patients, and biopsy alone in one patient) followed by radiation therapy to the craniospinal axis. The 5-year actuarial survival rate is 77% with a disease-free survival of 58%. Five patients have relapsed in the posterior fossa, one in the brain parenchyma, and two in osseous sites. Two of the local relapses occurred more than 4 years after initial treatment. Patients undergoing "total" resection of the tumor fared better than those with partial resection or biopsy only. Local failure was uncommon with posterior fossa doses greater than 55 Gy, and there was a trend toward better local control when the radiation therapy was completed in less than 7 weeks. The histologic indicators of poor outcome were necrosis, high mitotic index, and "classical" histologic appearance.

Adult↗

Assessment of renal function in the patient receiving chemotherapy.

With foresight, knowledge, and an awareness of the problem, nephrotoxicity associated with chemotherapy can be prevented or minimized, thereby avoiding irreversible renal failure or death. Careful assessment of those patients at risk for renal damage and the identification of early signs/symptoms of renal impairment are key steps in the prevention and early detection of renal dysfunction. The purpose of this article is to describe the clinical and laboratory manifestations of renal toxicity, as well as the nurse's role in the assessment of nephrotoxicity.

Antineoplastic Agents↗