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Biomedical subjects

M Conley

Publications and source records attributed to M Conley.

At least 19 recordsLinked to original sources
PubMed2002

Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age.

BACKGROUND: Ongoing clinical trials are investigating whether lowering plasma homocysteine reduces the risk of vascular disease. If so, food fortification with folic acid will be the likely result, and sub-optimal amounts are likely to be preferred, for safety reasons. Dose-finding studies are needed before the outcomes of these trials, to establish the benefits and risks of folic acid consumption over the widest intake range likely to be encountered. AIM: To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women. DESIGN: Double-blind, randomized placebo-controlled trial. METHODS: Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 microg/day of folic acid. Red-cell folate and plasma homocysteine were measured at baseline and after 10 weeks supplementation. RESULTS: Median red cell folate levels increased significantly in the 200 microg(p=0.0001) and 400 microg(p=0.0001) groups; but not in the placebo (0 microg) (p=0.25) or the 100 microg (p=0.5) groups. Only the 200 microg and the 400 microg groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 micromol/l (already optimally low) were removed from the analysis, there were significant plasma homocysteine decreases in all three treatment groups, but not the placebo group. DISCUSSION: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.

Adult↗
PubMed2002

239,240Pu and inorganic substances in aerosols from the vicinity of a waste isolation pilot plant: the importance of resuspension.

Aerosol samples were collected and analyzed to characterize the spatial and temporal variations in the concentrations of plutonium and selected inorganic substances in the atmosphere around the Waste Isolation Pilot Plant (WIPP). High-volume aerosol sampling was conducted at three sites: (1) On Site, (2) Near Field, and (3) Cactus Flats. 239,240Pu was determined by alpha spectrometry following chemical separations; mass loadings were determined gravimetrically. A separate set of low-volume aerosol samples was analyzed for major ions using ion chromatography and for trace elements by inductively-coupled plasma emission spectrometry and mass spectrometry. The average 239,240Pu activity concentrations in total suspended particle (TSP) samples (12 to 16 nBq m(-3)) were consistent with those previously reported, but they varied strongly with season, with the highest values generally in spring. Further, the 239,240Pu activity concentrations were comparable among the three sites, and therefore there was no evidence for elevated 239,240Pu activities due to WIPP operations. The fraction of the 239,240Pu activity concentrations in the PM10, samples (particles less than 10 microm diameter) relative to TSP was lower than the corresponding PM10/TSP ratios of either high-volume mass or several inorganics (sulfate, aluminum or lead), indicating that 239,240Pu tends to be on large particles. Aerosol mass loadings (microg m(-3)) and 239,240Pu activity concentrations were correlated for all sets of samples, but at On Site, the TSP samples showed higher mass to 239,240Pu ratios than the other sites. Thus activities or processes occurring at or near the WIPP site evidently produced aerosols that contributed to the mass loadings but contained less 239,244Pu than ambient aerosols. About 63% of the variability in 239,240Pu activity concentrations was explained by wind travel, sampling location, length of the sampling interval, and aerosol mass. 239,240Pu activity concentrations also were correlated with aluminum (an indicator of mineral dust), further implicating the resuspension of soils as an important determinant of 239,240Pu in aerosols. The 239,240Pu/Al ratios for the aerosols were higher than in soils, and this could be explained by the preferential binding of 239,240Pu to small soil particles that have large surface area to mass ratios and also have higher aluminum contents than larger particles.

Aerosols↗
PubMed1999

Thalamic and basal forebrain cholinergic connections of the rat posterior parietal cortex.

The thalamic connectivity and basal forebrain cholinergic input to the posterior parietal cortex (PPC) of Long-Evans rats was examined using combined retrograde tracing and immunocytochemical methods. As in previous studies, the PPC could be distinguished by its input from the lateral posterior, lateral dorsal, and posterior nuclei of the thalamus, but not the lateral geniculate nucleus or ventrobasal complex. These nuclei were also observed to receive reciprocal projections from the ipsilateral PPC. Cholinergic neurons innervating the PPC were primarily localized to the substantia innominata/nucleus basalis region. The implications of these data for possible functions of the cholinergic input to PPC are discussed.

Animals↗
PubMed1999

The influence of 5,10 methylenetetrahydrofolate reductase genotypes on enzyme activity in placental tissue.

OBJECTIVE: To study the effects of heterozygosity and homozygosity for the C677T mutation of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene on the activity of this enzyme in placental tissue from pregnancies not affected by neural tube defect. DESIGN: Placental tissue was genotyped for the C677T variants of MTHFR. Total enzyme activity and residual activity after heating to 46 degrees C for 5 minutes was then measured. SETTING: A teaching hospital. SAMPLE: Placental samples (n = 200), one from each of 200 uncomplicated term deliveries. MAIN OUTCOME MEASURES: Total and residual enzyme activity for MTHFR. RESULTS: Placentae heterozygous for the C677T mutation of the MTHFR gene had significantly lower total enzyme activity than those without the mutation; the lowest activity occurred in homozygotes for the mutation. The same pattern was seen in relation to enzyme activity after heating. CONCLUSION: This study demonstrates that reduced enzyme activity is associated with the C677T variant of MTHFR in placental tissue. This is an important metabolic step in folic acid metabolism and pro-

Biomarkers↗
PubMed1998

Low blood folates in NTD pregnancies are only partly explained by thermolabile 5,10-methylenetetrahydrofolate reductase: low folate status alone may be the critical factor.

Thermolabile 5,10-methylenetetrahydrofolate reductase (MTHFR) is the first folate-related variant to be associated with an increased risk of neural tube defects (NTDs). The variant causes high plasma homocysteine levels and reduced red cell folate (RCF) levels, both of which have also been linked to an increased risk of NTDs. We examined the relationship between folate status and presence of the common mutation MTHFR C677T in 82 NTD-affected and 260 control mothers. Homozygosity for the TT genotype was associated with very low folate status among both the cases (n = 13) and the controls (n = 21). However, after exclusion of TT homozygotes, only 10% of the remaining 240 controls had RCF levels less than 200 microg/L compared with 29% of the 69 cases (odds ratio, 3.67; 95% confidence interval, 1.88-7.18; P < 0.001), and those with RCF less than 150 microg/L had eight times higher risk of NTD than subjects with levels over 400 microg/L. Plasma homocysteine levels of non-TT cases were also higher than those of controls (P = 0.047). This study shows that homozygosity for the C677T MTHFR variant cannot account for reduced blood folate levels in many NTD-affected mothers. Thus, a strategy of genetic screening of all childbearing women for this variant would be ineffective as a method of primary prevention of NTDs. The data suggest that low maternal folate status is itself the major determinant of NTD risk, or else that other folate-dependent genetic variants confer risk through the reduction of folate levels. These results emphasize the importance of a food-fortification program as a population strategy for reducing the occurrence of NTDs.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1998

Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study.

Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters. All subjects were instructed to fast overnight for 10 to 12 hours. Three hundred sixty-one women were studied between 6 and 12 weeks of gestation. A median decrease in plasma glucose of 2 mg/dL was observed between weeks 6 and 10 (P=.007). In a smaller group of subjects evaluated through the third trimester, little further glucose reduction was observed. A reduction in glycosylated hemoglobin levels between 10 and 20 weeks (P=.002) followed the earlier reduction in first trimester glucose levels. Analysis by body mass index (BMI) showed a smaller first trimester reduction with increasing BMI, and none among severely obese women (BMI > 29.9 kg/m2). The decline in fasting plasma glucose in pregnancy begins early in the first trimester, well before fetal glucose requirements can contribute to the decline in the glucose level. Thereafter, plasma glucose levels decrease little. These results suggest that in the setting in which this study was performed (an overnight fast) maternal physiologic adjustments account for a reduction in plasma glucose early in the first trimester of pregnancy, and possibly even later in gestation as well.

Adult↗
PubMed1997

Minimum effective dose of folic acid for food fortification to prevent neural-tube defects.

BACKGROUND: Although a daily supplement of 400 micrograms folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 micrograms. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 micrograms/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. METHODS: We screened 323 women. 172 with red-cell folate between 150 micrograms/L and 400 micrograms/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 micrograms, 200 micrograms, or 400 micrograms daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. FINDINGS: There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 micrograms/L (95% CI 43-120) and 375 micrograms/L (354-444) in the 100 micrograms/day group, 130 micrograms/L (108-184) and 475 micrograms/L (432-503) in the 200 micrograms/day group, and 200 micrograms/L (125-312) and 571 micrograms/L (481-654) in the 400 micrograms/day group. INTERPRETATION: A fortification programme that delivered 400 micrograms folic acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 micrograms daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 micrograms daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD.

Adult↗
PubMed1996

Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects.

Considerable evidence suggests that various discrete nuclei within the amygdala complex are critically involved in the assignment of emotional significance or value to events through associative learning. Much of this evidence comes from aversive conditioning procedures. For example, lesions of either basolateral amygdala (ABL) or the central nucleus (CN) interfere with the acquisition or expression of conditioned fear. The present study examined the effects of selective neurotoxic lesions of either ABL or CN on the acquisition of positive incentive value by a conditioned stimulus (CS) with two appetitive Pavlovian conditioning procedures. In second-order conditioning experiments, rats first received light-food pairings intended to endow the light with reinforcing power. The acquired reinforcing power of the light was then measured by examining its ability to serve as a reinforcer for second-order conditioning of a tone when tone-light pairings were given in the absence of food. Acquisition of second-order conditioning was impaired in rats with ABL lesions but not in rats with CN lesions. In reinforcer devaluation procedures, conditioned responding of rats with ABL lesions was insensitive to postconditioning changes in the value of the reinforcer, whereas rats with CN lesions, like normal rats, were able to spontaneously adjust their CRs to the current value of the reinforcer. The results of both test procedures indicate that ABL, but not CN, is part of a system involved in CSs' acquisition of positive incentive value. Together with evidence that identifies a role for CN in certain changes in attentional processing of CSs in conditioning, these results suggest that separate amygdala subsystems contribute to a variety of processes inherent in associative learning.

Acoustic Stimulation↗
PubMed1996

Infectious processes: an infrequent cause of first trimester spontaneous abortions.

A systematic assessment of infections beginning early in pregnancy is necessary to determine the true role of infections in pregnancy loss, given that infections could readily arise only after fetal demise. To this end, we have prospectively determined the frequency of infections in pregnant women who were subjects in a multi-centre US study. Insulin-dependent diabetic subjects and controlled subjects were recruited either before conception (86%) or at the latest within 21 days of conception (14%). We collected data prospectively on all important risk factors and potential confounding variables, seeing 386 diabetic subjects weekly and 432 control subjects every other week during the first trimester. At each visit we inquired about untoward events and explicitly about fever or infections. We found no clinical evidence that infection occurred more often in the 116 subjects experiencing pregnancy loss as compared to the 702 having successful pregnancies. This held both for the 2 week interval in which a given loss was recognized clinically as well as in the prior 2 week interval. Similar findings were not only observed for both the control as well as diabetic subjects but also when data were stratified by genital infection only or by systemic infection only. Our prospective data suggest that the attributable risk of infection in first trimester spontaneous abortion is small.

Abortion, Spontaneous↗
PubMed1995

The acute immune response to exhaustive resistance exercise.

Ten young male adults (mean age 46.9 +/- 1.2 yrs) with 9.2 +/- 1.4 years of weight training experience and the ability to parallel squat at least 1.5 times their body mass were selected as subjects. The exercise session consisted of sets of 10 repetitions at 65% 1-RM of the parallel leg squat, with a cadence of one rep every 6 sec and 3 min rest between sets, to muscular failure. The average subject lifted a total of 9711 +/- 1576 kg during 98 +/- 14 reps for a total work output of 72.5 +/- 10.5 kJ before muscular failure occurred. Mean oxygen consumption during exercise was 1.58 +/- 0.06 l/min at 42.5 +/- 2.0% peak VO2. A strong leukocytosis, lymphocytosis, and lymphocytopenia, similar to what has been reported following high-intensity cardiorespiratory exercise, were measured following leg squat exercise. Con A-stimulated lymphocyte proliferation (unadjusted) rose 50% above preexercise levels (p = 0.07), but when these data were adjusted on a per T cell (CD3+) basis, no change from rest was observed. Natural killer cell cytotoxic activity (NKCA), when adjusted on a per NK cell (CD56+) basis, was decreased about 40% below preexercise levels for at least 2 h post-exercise. No significant increase in cortisol was seen after exercise, although norepinephrine and epinephrine increased moderately (465% and 133%, respectively), immediately following exercise. The data demonstrate that leg squat exercise to muscular failure results in a very similar immune response to that associated with intense endurance exercise, despite a lower mean oxygen consumption and only a moderate hormonal response.

Adult↗
PubMed1995

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Adult↗
PubMed1994

The delta (argF-lacZ)205(U169) deletion greatly enhances resistance to hydrogen peroxide in stationary-phase Escherichia coli.

In this study, we demonstrate that a strain bearing the delta (argF-lacZ)205(U169) deletion exhibits a high level of resistance to hydrogen peroxide compared with its undeleted parent. Our initial investigation of the mechanism behind the observed differences in peroxide resistance when parent and mutant strains are compared indicates that the parent strain carries a region near argF that is responsible for the H2O2-sensitive phenotype, which we have named katC. The H2O2 resistance phenotype of the delta katC [delta (argF-lacZ)205(U169)] mutant strain can be duplicated by Tn9 insertion in a specific locus (katC5::Tn9) which maps near argF. The increased H2O2 resistance of the delta katC and katC5::Tn9 mutant strains can be seen only when cells are grown to stationary phase; exponential-phase cells are unaffected by the presence or absence of katC. This H2O2 resistance mechanism requires functional katE and katF genes, which suggests that the mechanism of H2O2 resistance may involve the activity of the stationary-phase-specific catalase HPII. Cloning, DNA sequencing, and analysis of the katC5::Tn9 insertion allele in comparison with its parent allele implicate two insertion elements, IS1B and IS30B, and suggest that their presence sensitizes parent cells to H2O2.

Alleles↗
PubMed1993

Functional organization of the ventral lateral geniculate complex of the tree shrew (Tupaia belangeri): I. Nuclear subdivisions and retinal projections.

This is the first of two papers describing the organization and connections of the ventral lateral geniculate complex (GLv) in the tree shrew. Using a combination of Nissl, Golgi, histochemical, and immunocytochemical methods, we have identified two major divisions (lateral and medial) of GLv, both of which can be further subdivided. The lateral division contains three subdivisions, external, internal and intergeniculate leaflet. The medial division contains two subdivisions, medio-rostral and medio-caudal. All three lateral subdivisions receive input from the retina, the densest terminations being in the external subdivision and intergeniculate leaflet. These projections originate primarily from small retinal ganglion cells, although a few large retinal ganglion cells also project to GLv by way of collateral branches. Each subdivision of GLv has a distinct cytoarchitectonic and immunocytochemical make-up. In general, the level of immunoreactive endings for glutamic acid decarboxylase (GAD), leuenkephalin (ENK), and choline acetyltransferase (ChAT) parallels the distribution of retinal projections. Thus, all three markers are particularly dense in the external subdivision and the intergeniculate leaflet. Cell bodies immunoreactive for ENK are restricted to the external and intergeniculate leaflet subdivisions. The medial subdivisions stain relatively poorly for GAD, ENK, and ChAT, although each has other cytological features that differentiate them from the lateral subdivisions and the adjacent thalamic reticular nucleus.

Animals↗
PubMed1993

Functional organization of the ventral lateral geniculate complex of the tree shrew (Tupaia belangeri): II. Connections with the cortex, thalamus, and brainstem.

Connections of the ventral lateral geniculate complex (GLv) in the tree shrew were traced by anterograde and retrograde transport of WGA-HRP. The results buttress earlier findings that GLv in this species is composed of two main divisions, lateral and medial, each of which differs in its connections with the brainstem and cerebral cortex. The connections of the lateral division (GLv) suggest that it participates in visuosensory functions: it receives input from the retina, striate cortex, pretectum, and retino-recipient layers of the superior colliculus. These connections help clarify the identification of the internal and external subdivisions of GLv inasmuch as projections from both the superior colliculus and pretectum terminate in the external subdivision and each, in turn, receives a projection from the internal subdivision. Connections of the medial division suggest that this part of the nucleus is involved with visuomotor functions. Thus, the medio-caudal subdivision projects to the pontine nuclei, the prerubral field and the central lateral nucleus. The medio-caudal subdivision also receives projections from the lateral cerebellar nucleus, so that the GLv-ponto-cerebello-GLv loop involves mainly one subdivision of GLv. The medio-rostral subdivision receives projections from the pretectum and parietal cortex. Its output is directed primarily at the intermediate and deep layers of the superior colliculus. All of these targets of GLv, the pons, prerubral field, and deep layers of the superior colliculus, are known to play a role in the coordination of head and eye movements. Additional connections of GLv with the vestibular nuclei, intralaminar nuclei, hypothalamus, and facial motor nucleus are also described.

Animals↗
PubMed1993

Phenytoin and magnesium sulfate effects on fetal heart rate tracings assessed by computer analysis.

OBJECTIVE: To compare the effects of maternally administered phenytoin and magnesium sulfate on the fetal heart rate (FHR) using computer analysis. METHODS: Thirty-six nonlaboring preeclamptic women between 27-41 weeks' gestation were treated with either phenytoin or magnesium sulfate in a nonrandomized fashion. All fetuses were deemed to be well by traditional electronic-biophysical criteria. One-hour FHR recordings were analyzed by computer analysis before treatment. No other medications were administered. Tracings recorded 1 hour after drug administration were analyzed. Therapeutic serum levels were achieved in both groups before FHR tracings were reevaluated. Statistical analysis used paired Student t test, with significance set at P < or = .05. RESULTS: There were no differences in birth weight, gestational age, Apgar scores, or computer-analyzed FHR characteristics between the groups before treatment. Magnesium sulfate reduced significantly the frequency of accelerations of ten and 15 beats per minute; caused a 62% reduction in reactivity, defined as accelerations of 15 beats per minute in 20 minutes of FHR tracing (but no change in reactivity with accelerations of ten beats per minute); and reduced short- and long-term variability. Phenytoin reduced short-term variability only. CONCLUSION: Phenytoin does not confound the computer analysis of FHR tracings and may offer some advantage over magnesium sulfate when used for prophylaxis against eclampsia.

Diagnosis, Computer-Assisted↗
PubMed1992

Dendritic organization of class II (inter)neurons in the dorsal lateral geniculate nucleus of the tree shrew: observations based on Golgi, immunocytochemical, and biocytin methods.

In this report we examine the dendritic organization of putative interneurons (class II cells) in different layers of the dorsal lateral geniculate nucleus of the tree shrew. The results show that there is considerable morphological diversity within this class, but that two broad groups can be identified: neurons whose dendrites remain within a layer or its adjacent interlaminar zones (intralaminar class II cells); and neurons whose dendrites cross into an adjacent layer(s) (interlaminar class II cells). The majority of class II cells in every layer have intralaminar dendrites, some of which are oriented along a particular axis, and others that are organized radially. The paired layers (1 and 2, 4 and 5) contain a particular group of intralaminar class II cells that have radially organized dendrites and elaborate claw-like appendages. The dendrites of interlaminar class II cells are organized along lines of projection and extend across as many as four layers. These cells often reside close to or within the interlaminar zones. Overall, the organization of class II cells seems to follow a pattern similar to the class I (relay) cells identified previously. Most have intralaminar dendrites, which presumably underlie the fidelity of signals transmitted from the retina to a particular layer. However, there are also a number of other cells whose processes cross laminar borders, presumably to affect integrative functions within the nucleus.

Animals↗
PubMed1992

A projection from the parabigeminal nucleus to the pulvinar nucleus in Galago.

A projection from the parabigeminal nucleus (Pbg) to the striate-recipient zone of the pulvinar nucleus in the prosimian Galago was identified by anterograde and retrograde transport methods. In addition to the pulvinar nucleus, Pbg projections were found to terminate in layers 4 and 5 of the dorsal lateral geniculate nucleus and the central lateral nucleus. All three of these structures project to the superficial layers of the striate cortex. Similarities between the Pbg in mammals and the nucleus isthmi in nonmammals in connections and neurochemistry reinforce the idea that these two nuclei are homologous.

Animals↗