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Biomedical subjects

D E Fleming

Publications and source records attributed to D E Fleming.

At least 19 recordsLinked to original sources
PubMed2001

Sexual dimorphism and aromatase in the rat retina.

The present study: (a) determined the effects of both pre- and early postnatal androgen hormonal manipulation on retinal thickness, (b) examined the presence of the aromatase enzyme by immunocytochemistry in retinal tissue and (c) quantified aromatase activity in the rat retina. The results suggest that retinal thickness is influenced by perinatal hormone manipulation via aromatizable androgens that have implications for the sex differences seen in visual information processing and performance.

Androgen Antagonists↗
PubMed2001

Intracrystalline proteins and the hidden ultrastructure of calcium oxalate urinary crystals: implications for kidney stone formation.

The external appearance of urinary calcium oxalate (CaOx) crystals suggests that they are solid, homogeneous structures, despite their known association with proteins. Our aim was to determine whether proteins comprising the organic matrix of CaOx crystals are superficial or intracrystalline in order to clarify the role of urinary proteins in the formation of kidney stones. CaOx crystals were precipitated from centrifuged and filtered, or ultrafiltered, healthy human urine. They were then treated with dilute NaOH to remove bound proteins, partially demineralized with EDTA, or fractured and subjected to limited proteolysis before examination by low-resolution scanning electron microscopy or field emission scanning electron microscopy. Crystals precipitated from centrifuged and filtered urine had a complex interior network of protein distributed throughout the mineral phase, which appeared to comprise closely packed subcrystalline particles stacked in an orderly array among an amorphous organic matrix. This ultrastructure was not evident in crystals deposited in the absence of macromolecules, which were completely solid. This is the first direct evidence that crystals generated from cell-free systems contain significant amounts of protein distributed throughout a complex internal cribriform ultrastructure. Combined with mineral erosion in the acidic lysosomal environment, proteins inside CaOx crystals would render them susceptible to attack by urinary and intracellular renal proteases and facilitate their further dissolution or disruption into small particles and ions for removal by exocytosis. The findings also have broader ramifications for industry and the materials sciences, as well as the development and resorption of crystals in biomineralization systems throughout nature.

Adolescent↗
PubMed2001

Calibration and characterization of a digital X-ray fluorescence bone lead system.

Five different combinations of digital shaping parameters were tested for a newly assembled. 109Cd source, K X-ray fluorescence bone lead system. System calibration results are presented, along with analyses of measurement uncertainty and reproducibility obtained from repeat measurements of a bone phantom and a human tibia. Digital shaping parameters of 2.4 micros for a rise time/fall time and 1.2 micros for a flat top width were identified as superior. The digital system provided significant improvements in overall measurement precision, with gains of at least 25-35% over conventional system results.

Bone and Bones↗
PubMed2001

A comparative study of the adsorption of amino acids on to calcium minerals found in renal calculi.

To assess the binding of individual amino acids to the principal calcium minerals found in human kidney stones, the adsorption of 20 amino acids on to calcium oxalate monohydrate, CaHPO4*2H2O, Ca3(PO4)2 and Ca5(PO4)3OH crystals was determined over the physiological urinary pH range (pH 5-8) in aqueous solutions. All amino acids adsorbed most strongly at pH 5, and this decreased in all cases as the pH was increased. The amino acids which adsorbed most strongly were aspartic acid, glutamic acid and gamma-carboxyglutamic acid, with the last displaying the strongest affinity. All amino acids bound more avidly to calcium oxalate monohydrate than to any of the phosphate minerals. Adsorption on to CaHPO4*2H2O was generally higher than for Ca3(PO4)2 and Ca5(PO4)3OH, for which all amino acids, with the exception of gamma-carboxyglutamic acid, had only a weak affinity. The binding affinity of these acids is thought to be due to their zwitterions being able to adopt conformations in which two carboxyl groups, and possibly the amino group, can interact with the mineral surface without further rotation. The strong binding affinity of di-and tri-carboxylic acids for calcium stone minerals indicates that proteins rich in these amino acids are more likely to play a functional role in stone pathogenesis than those possessing only a few such residues. These findings, as well as the preferential adsorption of the amino acids for calcium oxalate monohydrate rather than calcium phosphate minerals, have ramifications for research aimed at discovering the true role of proteins in stone formation and for potential application in the design of synthetic peptides for use in stone therapy.

Adsorption↗
PubMed2000

Pre- or postnatal testosterone and flutamide effects on sexually dimorphic nuclei of the rat hypothalamus.

Utilizing the sexually dimorphic nature of hypothalamic nuclei, a determination of the effects of pre- or postnatal flutamide and testosterone treatments were examined in male and female rats. Statistical analysis compared treatments, sex, and time of injection in terms of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) volumes and lengths. The present findings establish that pre- or postnatal hormonal environments are crucial in influencing sexual morphology on the developing brain.

Androgen Antagonists↗
PubMed2000

The hole truth: intracrystalline proteins and calcium oxalate kidney stones.

The ultimate aim of our research is to understand the role of macromolecules in the formation of human kidney stones, particularly their interactions with calcium oxalate (CaOx) crystals. The invariable association of stones with proteins raises the possibility that proteins play a role in their formation, similar to the role of proteins in healthy biomineralization. Do these proteins induce mineralization? Are they merely a response to the disease process? Or are they protective molecules that were overwhelmed by mineral supersaturation? A protein of particular interest is fragment 1 (F1) of prothrombin. We have shown that mRNA for prothrombin is present in the kidney. Because the F1 fragment of prothrombin present in urine is slightly different from that found in the blood, we refer to this protein as "urinary prothrombin fragment 1" (UPTF1). Available evidence suggests that the kidney manufactures the protein for protection against stone disease and that the protein has a directive role in stone formation. We now have evidence that proteins are interred within CaOx crystals precipitated from human urine, where it is distributed in continuous channels. These proteins could facilitate crystal deconstruction and removal after attachment to the renal epithelium and endocytosis. We suspect that the formation of CaOx crystals in the urine is a normal process designed to permit harmless disposal of an excess of calcium, oxalate, or both. The incorporation of proteins provides a second line of defense against stone formation by enabling the destruction and removal of retained crystals. Understanding the basic molecular strategies by which plants produce protein-containing CaOx crystals may provide insight into human CaOx stone formation.

Calcium Oxalate↗
PubMed1999

The O'Flaherty model of lead kinetics: an evaluation using data from a lead smelter population.

The O'Flaherty model of lead kinetics is a physiologically based computer model of lead disposition in humans. The model is based on an age-dependent approach to human growth, with particular attention devoted to bone metabolism. As such, model output is well suited for comparison with noninvasive bone lead measurements made via X-ray fluorescence. A subset of workers from a lead smelter population were selected for an initial evaluation of the O'Flaherty model. Detailed blood lead records were used to define input. Simulated bone lead and blood lead output were compared with observation, enabling a refinement of model parameters. A revised version of the O'Flaherty model was then evaluated for the smelter population as a whole. Previously observed trends for the accumulation of lead in cortical bone and the release of lead from bone stores were well explained by the revised model. Model predictions for the accumulation of lead in trabecular bone were not in accord with observed levels in the calcaneus. Model results from the smelter population are consistent with the hypothesis that a polymorphism in the delta-aminolevulinate dehydratase enzyme modifies the kinetics of lead in humans. Further refinements are suggested, which may enhance the ability of the model to explain the underlying relationships between lead exposure and the distribution of lead in the body.

Aging↗
PubMed1999

Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in control and prenatally stressed male rats.

The present study was designed to examine the effects of prenatal stress on the morphological development of sexually dimorphic structures in the anterior hypothalamus in male rats and to determine if there is a relationship between morphologic development of the brain and copulatory behavior in individual animals. Dams in the stress group were subjected to treatments of heat-light restraint during the third trimester of gestation (day 14 to parturition) three times daily for 45-min periods. At 90 days of age, prenatally stressed and control male offspring were tested during the dark cycle for spontaneous male sexual behavior. Volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the anteroventral periventricular nucleus (AVPV) were measured. Comparisons were made between copulatory behavior and hypothalamic nuclear volumes. SDN-POA volumes were significantly reduced (feminized; males have a larger SDN-POA than females) in prenatally stressed males that did not copulate, whereas, SDN-POA volumes in prenatally stressed males that copulated were not altered. The few control males that did not copulate (sexually non-active) also had significantly reduced SDN-POA volumes compared to the control males that did copulate (sexually active). The volume of the AVPV was significantly increased (feminized; males have a smaller AVPV than females) in prenatally stressed males that were sexually non-active compared to AVPV volumes in sexually active males. The results obtained in this study provide a strong positive relationship between sexual behavior and the morphology of the two sexually dimorphic structures measured.

Animals↗
PubMed1999

Effects of pattern, spatial frequency, number, and rate of stimulus presentation on the accuracy of detection.

Brief trains of pulsed stimuli were used to assess whether magnocellular or parvocellular visual pathways could be differentiated perceptually. Trains of either one to four sine-wave, square-wave, or checkerboard gratings were presented at three temporal and two spatial frequencies to six observers. The task of the observer was to report the perceived number of stimuli (gratings) in a train. The difference between actual number and perceived number of gratings was recorded as an error score. It was found that neither the pattern nor the spatial frequency of the gratings significantly affected perceptual accuracy. On the other hand, the number of gratings in a train and the interstimulus interval between gratings produced significant differences. Perceptual accuracy was greater when lower numbers of gratings in a train were presented with longer interstimulus intervals. The observers typically reported fewer stimuli than were presented. The source of the discrepancy is discussed in terms of a light adaptive process initiated in the retina.

Adolescent↗
PubMed1998

Effects of sexual behavioral manipulation on brain plasticity in adult rats.

The purpose of the present study was to determine the effects of sexual behaviorial manipulation on brain plasticity in adult male rats. Adult male Sprague-Dawley rats that copulated during male sexual behavior testing were divided into four groups: control male; gonadectomized (Gdx) male; sexually active male; and sexually nonactive male. Female animals were used as an additional control group. At the end of a 12-week experimental period, the animals were again tested for male sexual behavior and tested for sexual motivation. Sexual behavior manipulations over the 12-week period resulted in significant differences in mount latency, mount frequency, intromission latency, intromission frequency, ejaculation latency, and the postejaculation interval. In the motivation test, significant differences in the number of approaches, contacts, and crossings of an electrified grid separating the test animal from a receptive female were also observed. Sexually dimorphic nucleus of the preoptic area (SDN-POA) volumes in sexually nonactive males were significantly smaller than in control males or sexually active males. Anteroventral periventricular nucleus (AVPV) volumes in the male groups were not significantly altered by sexual behavioral manipulations, however, the nonactive AVPV vol. was the only vol. not significantly different from the control female vol. These data demonstrate that in the adult rat, sexual behavioral manipulations resulted in significant alterations in behavior and in the vol. of the SDN-POA and that the effect of sexual behavior on the AVPV needs to be further investigated.

Animals↗
PubMed1998

Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers.

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.

Amino Acid Sequence↗
PubMed1997

Accumulated body burden and endogenous release of lead in employees of a lead smelter.

Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.

Adult↗
PubMed1995

The hormone-sensitive early postnatal periods for sexual differentiation of feminine behavior and luteinizing hormone secretion in male and female rats.

The purpose of this study was to determine the duration of the hormone-sensitive postnatal period during which a single injection of testosterone propionate (TP) influences feminine behavior and luteinizing hormone (LH) secretion in male and female rats. Male pups were castrated on the day of birth (day 1) between 6 and 12 h postpartum. On postnatal day 3, 4, 5, 6, 7, 8, or 9 female pups and castrated males (fales) were injected subcutaneously with testosterone propionate (TP-500 micrograms). The females were laparotomized at 60 days of age, and ovarian tissue was removed for histological analysis. Female behavior was evaluated at 100 days of age. At 150 days of age, the ability of steroids to facilitate LH secretion was determined. Tests for lordosis indicated a diminished lordotic quotient (LQ) with both females and fales treated with TP on postnatal day 3, 4, 5, 6, or 7. On day 8 or 9, however, the lordotic response was at control levels. Females in all TP treated groups had significantly reduced number of corpora lutea. Females and fales treated with TP on postnatal day 3, 4, 5, 6, 7, 8, or 9 failed to exhibit an LH surge as adults. The results indicate that the neural control of feminine behavior (LQ) is hormone-sensitive to a single injection of TP up through the 7th day of postnatal life, whereas the neural substrate regulating LH secretion was sensitive in the present study at least up through day 9 in both fales and females.

Animals↗
PubMed1991

Changes in open-field behavior of rats following spinal nerve root sectioning.

The open-field behavior of of 30 laboratory albino rats was measured after selective unilateral sectioning of either the L2, L3, L4 or L5 spinal nerve root using a novel abdominal entry. Although treated subjects displayed observable motor dysfunction of the operated limb, no differences were found in open-field ambulation, rearing, defecation or urination based either on the level of the sectioned nerve root or on the day the behavior was measured, suggesting that there was an effect of the treatment not measurable by standard statistical procedures, quite possibly due to the small sample size.

Animals↗
PubMed1989

Fetal male masculinization in control and prenatally stressed rats.

The present experiments were designed to test the hypothesis that males in utero masculinize the development of other males. This effect was examined during fetal development in males from control and prenatally stressed rats. A code identified the number of cervical-flanking males between the target male and the cervical end of the uterus. The male parameters morphology (anogenital distance) and body, adrenal, and testis weights were recorded on the eighteenth and twentieth gestational days and categorized by the cervical-flanking male classification. At Day 18, control fetuses with two cervical-flanking males in utero displayed significantly greater anogenital distance values than did males with no cervical-flanking male. At Day 20, control fetuses with two cervical-flanking males had testicular weights significantly greater than those of fetuses with one or zero cervical positioned male. Prenatal stress markedly impaired male fetal development at gestational Days 18 and 20 while suppressing the cervical-flanking male effect. These results confirm and extend previous data that indicate: (a) prenatal stress disrupts normal fetal development, resulting in long-term changes; and (b) androgens via a cervical-flanking blood-flow mechanism influence littermate morphology and sexual development during the prenatal period. Our findings also demonstrate that a general masculinizing effect could not be made across the measured male parameters since the effect of males positioned at the cervical-flanking region in utero appears to be dependent upon maternal sources of variance. Finally, androgens prenatally have an apparent positive interaction with somatic growth.

Adrenocorticotropic Hormone↗
PubMed1987

The effects of bilateral and unilateral frontal lesions on visual cortical hypersynchronous bursting and behavioral activity.

Photically evoked after-discharge (PhAD) bursting was examined in albino rats following either bilateral or unilateral dorsal frontal lesions. The initial effect of either type of frontal lesion was to significantly suppress PhAD occurrence. However, after repeated exposure to the PhAD recording environment no difference could be seen between the lesioned and control animals. In addition, no difference in PhAD could be detected between the two visual cortices in any of the groups. Spontaneous alternation and open-field activity were also tested. Both frontally lesioned groups of animals were significantly more active than control animals in the initial stages of testing. These findings indicate that the frontal cortex can inhibit brain stem mechanisms which are responsible for behavioral arousal and the modulation of hypersynchronous bursting in the cortex. However, because no difference was seen between the two visual cortices in any of the groups, it is suggested that this mechanism is not a strictly unilateral mechanism.

Animals↗