Biomedical subjects

R J McMahon

Publications and source records attributed to R J McMahon.

At least 19 recordsLinked to original sources

PubMed2004

Balance and serum concentration of biotin in sheep fed alfalfa meal-based diets with increasing level of concentrate.

The objective of this study was to test the hypothesis that serum biotin concentration and biotin balance (consumed - [urinary output + fecal output]) measured as total avidin-binding substances (biotin + biotin metabolites) are responsive to changes in the proportions of dietary alfalfa meal and concentrate fed to sheep. Eight sheep (initial BW = 40 kg) consumed a pelleted alfalfa meal-based diet that had 95:5, 48:52, 23:77, or 9:91% alfalfa meal:concentrate ratios (DM basis) in a replicated 4 x 4 Latin square design with 20-d periods (10 d of acclimation, 7 d of adaptation, and a 3-d collection period with jugular blood drawn on the last day). Replacing alfalfa meal with concentrate in the pelleted diets decreased dietary concentrations of biotin proportionally. As the percentage of alfalfa meal in the diet decreased, there was a linear decrease in daily DM intake (1,128 to 901 g of DMI/d; P < 0.01), with a linear (P < 0.01) and quadratic (P < 0.01) increase in the apparent total-tract DM digestibility of diets (51.0 to 80.0%). The biotin consumed decreased with alfalfa meal proportion in the diet (linear, P < 0.01). Both fecal biotin concentration (linear, P < 0.01) and fecal biotin output (quadratic, P < 0.05) increased, reaching peaks at 23% alfalfa meal. Fecal biotin output was not correlated with biotin intake, DMI, or intake of digestible DM. Mean urinary output, urinary biotin concentration, urinary biotin output, and serum biotin concentration were not affected by treatments. Means of biotin balance were negative and revealed the same trends among treatments as did fecal output. Biotin balance was a quadratic (P < 0.05) function of decreasing alfalfa meal in the diet, with more negative values at the alfalfa meal:concentrate ratio of 23:77. Results suggest that the greatest synthesis of biotin in the total digestive tract occurs with diets of either 52 or 77% concentrate for sheep; however, research addressing the significance of biotin metabolites on biotin balance and plasma biotin pool is needed.

Animal Feed↗

PubMed2002

Differentiating anxious, aggressive, and socially competent preschool children: validation of the Social Competence and Behavior Evaluation-30 (parent version).

The present study examined the factor structure, internal consistency, and construct validity of the parent version of the Social Competence and Behavior Evaluation-30 for preschoolers (SCBE-30; LaFreniere, P. J. (1990). Social competence and behavior evaluation-30. Unpublished measure.), an adaptation of the validated teacher version of the same measure (LaFreniere & Dumas, Psychol. Asses. 8 (1996) 369). The parent version of the SCBE-30 is a 30-item Likert rating scale questionnaire designed to assess patterns of anxiety/withdrawal, anger/aggression, and social competence. Principal components analysis was used to identify the factor structure of the parent version of the SCBE-30 (N = 218 preschool children). To assess construct validity, a compliance task was utilized to determine whether children identified as high on anxiety/withdrawal, anger/aggression, or social competence with the parent version of the SCBE-30 (n = 20 for each group) could be distinguished behaviorally on several observational variables. Principal components analysis identified three factors accounting for 44% of the variance. Ten items positively loaded onto each factor and matched conceptual expectations. A between-subjects MANOVA demonstrated significant group differences in observed child behaviors including compliance, noncompliance, subtypes of noncompliance, and aversive behavior. Results of the current study suggested that the parent version of the SCBE-30 demonstrated both internal consistency and construct validity, and findings paralleled many of the results from LaFreniere and Dumas' validation of the teacher version of the SCBE-30.

Aggression↗

PubMed2001

Microwave spectra and molecular structures of (Z)-pent-2-en-4-ynenitrile and maleonitrile.

Accurate equilibrium structures have been determined for (Z)-pent-2-en-4-ynenitrile (8) and maleonitrile (9) by combining microwave spectroscopy data and ab initio quantum chemistry calculations. The microwave spectra of 10 isotopomers of 8 and 5 isotopomers of 9 were obtained using a pulsed nozzle Fourier transform microwave spectrometer. The ground-state rotational constants were adjusted for vibration-rotation interaction effects calculated from force fields obtained from ab initio calculations. The resultant equilibrium rotational constants were used to determine structures that are in very good agreement with those obtained from high-level ab initio calculations (CCSD(T)/cc-pVTZ). The geometric parameters in 8 and 9 are very similar; they also do not differ significantly from the all-carbon analogue, (Z)-hex-3-ene-1,5-diyne (7), the parent molecule for the Bergman cyclization. A small deviation from linearity about the alkyne and cyano linkages is observed for 7-9 and several related species where accurate equilibrium parameters are available. The data on 7-9 should be of interest to radioastronomy and may provide insights on the formation and interstellar chemistry of unsaturated species such as the cyanopolyynes.

Journal Article↗

PubMed2001

The elusive benzocyclobutenylidene: a combined computational and experimental attempt.

Ab initio and density functional theory calculations predict that benzocyclobutenylidene (1) has a singlet ground state in contrast to the parent phenylcarbene and many other simply substituted arylcarbenes. Calculations also predict that 1 should lie in a relatively deep potential well, while its triplet state is 14.5 kcal mol(-)(1) higher in energy. However, attempts to observe 1 directly by photolysis of two different nitrogenous precursors were not successful. Irradiation of diazobenzocyclobutene (7) (lambda > 534 nm or lambda > 300 nm) or azibenzocyclobutene (10) (lambda > 328 nm) in Ar matrixes at 10 K leads to the formation of the strained cycloalkyne 7-methylenecyclohepta-3,5-dien-1-yne (3). (13)C-Labeled 3 was also prepared in a similar manner. There is very good agreement between experimental IR spectra and computationally derived harmonic vibrational frequencies for 3 and [(13)C]-3 and excellent agreement between observed and calculated isotopic shifts. Prolonged short-wavelength irradiation converts 3 into benzocyclobutadiene (5). Phenylacetylene (6) and benzocyclobutadiene dimer (11) were identified as products arising from flash vacuum pyrolysis of diazirine 10 at 500 degrees C.

Journal Article↗

PubMed2001

Structure and variability in the developmental trajectory of children's externalizing problems: impact of infant attachment, maternal depressive symptomatology, and child sex.

This study explores the developmental trajectory of externalizing problems in a sample of 101 children of adolescent mothers from preschool through third grade using hierarchical linear models (HLM). First, a detailed assessment of the structure of the developmental trajectory of externalizing problems is provided. Second, the impact of three risk factors (infant attachment, maternal depressive symptomatology, and child sex) on the developmental course of externalizing problems is assessed. Both avoidant and disorganized attachment and higher levels of maternal depressive symptomatology were associated with higher levels of externalizing problems at 9 years of age. Girls also showed higher externalizing problems relative to their same-sex peers than did boys. In addition, maternal depressive symptomatology related to the rate of change in these problems over time: the greater the mother's depression, the faster externalizing problems tended to increase. Although the overall level of maternal depressive symptomatology was related to children's externalizing problems for secure, avoidant, and disorganized groups, changes in maternal depressive symptomatology over time predicted levels of externalizing problems only for children with avoidant insecure attachments.

Child Behavior↗

PubMed2000

L-type Ca(2+) channel-mediated Zn(2+) toxicity and modulation by ZnT-1 in PC12 cells.

In view of evidence that Zn(2+) neurotoxicity contributes to some forms of pathological neuronal death, we developed a model of Zn(2+) neurotoxicity in a cell line amenable to genetic manipulations. Exposure to 500 microM ZnCl(2) for 15 min under depolarizing conditions resulted in modest levels of PC12 cell death, that was reduced by the L-type Ca(2+) channel antagonist, nimodipine, and increased by the L-type Ca(2+) channel opener, S(-)-Bay K 8644. At lower insult levels (200 micrometer Zn(2+)+Bay K 8644), Zn(2+)-induced death appeared apoptotic under electron microscopy and was sensitive to the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-CH(2)F (Z-VAD); at higher insult levels (1000 microM+Bay K 8644), cells underwent necrosis insensitive to Z-VAD. To test the hypothesis that the plasma membrane transporter, ZnT-1, modulates Zn(2+) neurotoxicity, we generated stable PC12 cell lines overexpressing wild type or dominant negative forms of rat ZnT-1 (rZnT-1). Clones T9 and T23 overexpressing wild type rZnT-1 exhibited enhanced Zn(2+) efflux and reduced vulnerability to Zn(2+)-induced death compared to the parental line, whereas clones D5 and D16 expressing dominant negative rZnT-1 exhibited the opposite characteristics.

Animals↗

PubMed2000

Glucose deprivation does not affect GLUT1 targeting in 3T3-L1 adipocytes.

We have previously demonstrated that glucose deprivation alters the glycosylation of the GLUT1 glucose transporter in 3T3-L1 adipocytes. Many aberrantly glycosylated proteins are retained in the endoplasmic reticulum by interaction with chaperones. Herein, we use three independent procedures to show that GLUT1 is targeted to the plasma membrane, despite alterations in glycosylation. While earlier experiments revealed that plasma membrane targeting of aglyco GLUT 1 transporter was significantly reduced, our data show for the first time that altered glycosylation provides sufficient information to drive appropriate trafficking.

3T3 Cells↗

PubMed2000

Integrative aspects of zinc transporters.

Cells maintain zinc concentrations with relatively narrow limits. Nevertheless, physiologically relevant changes in free Zn(II) pools or changes in Zn bound to specific ligands or within vesicles may occur without a major change in total cellular zinc concentrations. The task of maintaining such levels rests in part with zinc transporter proteins. The genes for some putative zinc transporters have recently been cloned. As of this time, most have not been directly shown to transport zinc in functional studies, albeit evidence is strong that they have such a function. Zinc transporter (ZnT)-1 was identified as a rescue agent for cells maintained in very high extracellular zinc conditions; therefore, ZnT-1 has been suggested to function as an exporter. ZnT-1 is expressed in a variety of tissues, including intestine, kidney and liver. Intestinal expression is regional, being much greater in duodenum and jejunum and in villus versus crypt cells. Immunolocalization places ZnT-1 at the basolateral membrane of intestinal enterocytes and epithelial cells of the distal renal tubules. Regulation of ZnT-1 mRNA and ZnT-1 protein does not change markedly with changes in dietary zinc level except when a large single oral zinc supplement is provided. ZnT-1 is induced by transient ischemia of the forebrain. ZnT-2 and ZnT-3 may function in tissue-specific vesicular zinc transport. ZnT-4 is believed to be abundant in mammary gland and may be associated with zinc secretion into milk. A mutation of the ZnT-4 gene may account for the lethal milk (lm) syndrome. The putative zinc transporters identified thus far appear to have characteristics commensurate with functions in integrative zinc acquisition and homeostasis.

Animals↗

PubMed2000

Parenting practices and child disruptive behavior problems in early elementary school. Conduct Problems Prevention Research Group.

Examined the hypothesis that distinct parenting practices may be associated with type and profile of a child's disruptive behavior problems (e.g., oppositional, aggressive, hyperactive). Parents of 631 behaviorally disruptive children described the extent to which they experienced warm and involved interactions with their children and the extent to which their discipline strategies were inconsistent and punitive and involved spanking and physical aggression. As expected from a developmental perspective, parenting practices that included punitive interactions were associated with elevated rates of all child disruptive behavior problems. Low levels of warm involvement were particularly characteristic of parents of children who showed elevated levels of oppositional behaviors. Physically aggressive parenting was linked more specifically with child aggression. In general, parenting practices contributed more to the prediction of oppositional and aggressive behavior problems than to hyperactive behavior problems, and parenting influences were fairly consistent across ethnic groups and sex.

Age Factors↗

PubMed1999

Longitudinal assessment of the low-end specificity of maternal reports of depressive symptoms.

Recent studies have raised concerns about the specificity of self-report measures of depression with respect to low-end scores. Because of the high face validity of measures such as the Beck Depression Inventory, it is suspected that extremely low scores may reflect individuals who may harbor depressive symptoms or other psychological abnormalities, yet are inclined to 'fake-good', or respond in a socially desirable manner on the BDI. The presence of this phenomenon was tested in a sample of adolescent mothers who were assessed at four time points over 8 years. It was hypothesized that low-scoring mothers (compared with medium- and high-scoring mothers) would have more negative outcomes on a variety of self-report and observational measures of parenting, as well as have children with more negative outcomes on adjustment and behavior. This study employed multiple assessments, multiple informants and multiple domains of functioning. The analyses controlled for the possible effects of social desirability and demographic differences between the depression groups. The hypotheses were not supported. The majority of analyses found no differences between the groups; where differences did exist, there were no indications that the low-scoring group was at a disadvantage to the medium or high scoring groups.

Adolescent↗

PubMed1999

Recurrent headache in adolescents: nonreferred versus clinic population.

OBJECTIVE: To compare headache activity, psychosocial measures, and cold pressor response between referred and nonreferred adolescents with frequent headache. DESIGN: Thirteen boys and 19 girls with a mean age of 13.4 +/- 0.9 years who had been referred to a hospital-based behavioral treatment program for recurrent headache were compared with an age- and sex-matched school-based population of nonreferred students consisting of 31 adolescents with frequent headaches and 32 adolescents with infrequent or no headaches. All subjects completed the Spielberger State-Trait Anxiety Inventory/Trait form, the Children's Depression Inventory, the Childhood Somatization Inventory, and measures of headache activity and related functional disability. Additionally, all subjects reported interval discomfort scores on a 40-second cold pressor test with arm immersion in a 10 degrees +/- 1 degree C cold water bath. RESULTS: Subjects from both headache groups reported significantly more anxiety than those with infrequent or no headaches. The school-based nonreferred adolescents reported more depressive symptoms than the clinic-based referred subjects. In addition, the latter group reported headaches of longer duration and more school days missed due to headaches than both other groups. Whereas school-based subjects and those with infrequent or no headaches reported relatively low initial cold pressor test scores and gradually reported increasing scores with time, clinic-based subjects rated their discomfort as high at the initial interval report and maintained high levels throughout the test. No differences in somatization were found among groups. CONCLUSION: Although adolescents who seek behavioral treatment for recurrent headache do not report more psychological symptoms than nonreferred adolescents with frequent headaches, they report headaches of longer duration, miss more school days due to headache, and report higher initial sustained discomfort scores to a standardized noxious stimulus.

Adaptation, Psychological↗

PubMed1999

Child and adolescent psychopathology as risk factors for subsequent tobacco use.

A growing body of research suggests that a number of types of psychopathology that occur during childhood and adolescence are also associated with an increased risk for tobacco use. This paper assesses the relationship between several types of child and adolescent psychopathology and subsequent tobacco use. The types of psychopathology that are discussed include 'externalizing' disorders such as conduct problems and attention-deficit/hyperactivity disorder (ADHD), and 'internalizing' disorders such as depression and anxiety disorders. The strongest evidence for connections between child and adolescent psychopathology and subsequent tobacco use is for conduct problems, ADHD, and depression. There is much weaker support for a connection between anxiety disorders and tobacco use. The relationships between conduct problems and ADHD (which frequently co-occur) and subsequent tobacco use are quite robust. Possible explanations of the relationships between conduct problems, ADHD, and tobacco use are presented. There appears to be a bidirectional relationship between depression and tobacco use; i.e., each has a comparable probability of preceding the other. Areas of particular importance are: (a) the effects of various psychopathologies on various aspects of tobacco use; (b) the role of comorbid psychopathologies; (c) identification of protective factors; (d) the effects of moderators (e.g., gender, ethnicity); (e) mechanisms and processes ('active ingredients') associated with various psychopathologies; (f) implications for intervention; and (g) possible cohort effects.

Adolescent↗

PubMed1998

Regulation of the zinc transporter ZnT-1 by dietary zinc.

The understanding of mechanisms controlling zinc absorption and metabolism at the molecular level has advanced recently. Kinetics of zinc transport have been investigated for many years, but only recently have genes coding for proteins thought to be involved in the transport process been cloned. Four putative zinc transporters, known as ZnT-1 through ZnT-4, have now been described. Among these transporters, only ZnT-1 is ubiquitously expressed. In this report, we examine the pattern of ZnT-1 expression in the intestine and analyze the regulation of ZnT-1 by dietary zinc in both the intestine and liver. Immunofluorescence demonstrated that intestinal ZnT-1 was most abundant at the basolateral surface of enterocytes lining the villi of the duodenum and jejunum. By Western blot analysis, intestinal and liver ZnT-1 protein migrated as a 42- and 36-kDa protein, respectively. Dietary zinc supplementation elevated the level of intestinal ZnT-1 mRNA and protein approximately 50% and 10%, respectively, but had no effect in the liver. In response to an acute oral zinc dose, the level of intestinal ZnT-1 mRNA was up-regulated 8-fold, without a corresponding increase in ZnT-1 protein. Conversely, the acute oral dose did not affect liver ZnT-1 mRNA, but resulted in a 5-fold increase in liver ZnT-1 protein. These results represent studies on the expression of intestinal and hepatic ZnT-1 in an intact animal model. The data suggest that ZnT-1 is at least part of the mechanism by which dietary zinc is absorbed and that, despite the zinc responsiveness of the ZnT-1 gene, additional factors may be regulating the steady-state level of ZnT-1 transporter protein.

Animals↗

PubMed1998

Parental monitoring and the prevention of child and adolescent problem behavior: a conceptual and empirical formulation.

The present report accomplishes three goals. First, to provide an empirical rationale for placing parental monitoring of children's adaptations as a key construct in development and prevention research. Second, to stimulate more research on parental monitoring and provide an integrative framework for various research traditions as well as developmental periods of interest. Third, to discuss current methodological issues that are developmentally and culturally sensitive and based on sound measurement. Possible intervention and prevention strategies that specifically target parental monitoring are discussed.

Adolescent↗

PubMed1998

Mammalian zinc transporters.

Genes that are involved in mammalian zinc transport recently have been cloned. These all predict proteins with multiple membrane spanning regions, and most have a histidine-rich intracellular loop. ZnT-1 was the first cloned and is associated with zinc efflux. It is found in all tissues examined, and, at least in some, ZnT-1 expression is regulated by dietary zinc intake. In enterocytes of the small intestine and renal tubular cells, ZnT-1 is localized to the basolateral membrane, suggesting an orientation that is consistent with zinc absorption/retention. ZnT-2 is also an exporter and may be involved in zinc efflux or uptake into vesicles in intestine, kidney, and testis. ZnT-3 is involved in zinc uptake into vesicles in neurons and possibly in testis. ZnT-4 is also an exporter and is highly expressed in mammary gland and brain. The divalent cation transporter 1 (DCT1) is regulated by iron, but exhibits transport activity for a number of trace elements including zinc. Description of a family of zinc transporters bridges the integrative and reductionist approach to the study of zinc metabolism. Other members of this transporter family may emerge. Many of these may be regulated by zinc, and some may respond to immune challenge, oxidative stress, and competing metals in the dietary supply. Collectively, description of transporters that influence cellular zinc uptake and efflux will provide a clearer understanding of the molecular events that regulate zinc absorption and homeostasis.

Animals↗

PubMed1998

Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression.

A role for metallothionein in intestinal zinc absorption has been the subject of considerable debate. If metallothionein affects zinc absorption, then those factors that induce metallothionein synthesis (e.g., heavy metals, hormones) should alter zinc absorption and homeostasis. The present studies used metallothionein transgenic mice (overexpressing) and metallothionein knockout mice (no expression of metallothionein-1 or metallothionein-2) to examine directly the effects of metallothionein on zinc absorption, independent of secondary effects that could be caused by metallothionein inducers. Zinc absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by feeding tube to metallothionein transgenic and metallothionein knockout mice and measuring the serum zinc concentration. Two hours after the dose, the serum zinc concentration was 2.3 times higher in metallothionein knockout mice than in their control strain. Conversely, the concentration was elevated only one third as much in the metallothionein transgenic mice as in their controls after the zinc dose. We found that the serum zinc concentration was inversely related to the level of metallothionein protein. The intestinal zinc content was higher in the metallothionein knockout mice, however, suggesting that metallothionein did not reduce zinc absorption by simply sequestering zinc in the mucosa. The expression of the zinc transporter ZnT-1 was directly related to the serum zinc level and was independent of the level of metallothionein. These results further support metallothionein as an important component for reducing the efficiency of zinc absorption at elevated zinc intakes.

Animals↗

PubMed1996

Differential regulation of GRP78 and GLUT1 expression in 3T3-L1 adipocytes.

We tested the hypothesis that the constitutive glucose transporter (GLUT1) in 3T3-L1 adipocytes belongs to the family of glucose-regulated proteins which are transcriptionally regulated by glucose deprivation. Using cDNA probes for both GRP78 (BiP) and GLUT1, we show that the level of GRP78 mRNA increased by 15-fold within 24 h of glucose deprivation with little change in GLUT1 mRNA. The elevated GRP78 mRNA in turn led to a time-dependent increase in GRP78 protein. While glucose deprivation did not alter the expression of the normal glycoform of GLUT1, a lower molecular weight glycoform accumulated with extended deprivation. Mannose and fructose, but not galactose, prevented the induction of GRP78 and accumulation of the abnormal GLUT1. Because GRP78 acts as a chaperone in other cell systems, we also sought evidence to support this activity in 3T3-L1 adipocytes. Using the technique of co-immunoprecipitation, we demonstrate that GRP78 bound several proteins unique to the glucose-deprived state. No deprivation-specific proteins could be detected in association with GLUT1. These data lead us to conclude that GLUT1 does not display characteristics of the glucose-regulated proteins, at least in 3T3-L1 adipocytes, a widely used model for differentiation, hormone action, and nutrient control. However, the mechanisms for activating traditional members of this family appear intact.

3T3 Cells↗

PubMed1996

Glycogen: a carbohydrate source for GLUT-1 glycosylation during glucose deprivation of 3T3-L1 adipocytes.

In 3T3-L1 adipocytes, the glycosylation of the GLUT-1 transporter is altered beyond 12 h of glucose deprivation. To determine whether glycogen degradation provides substrate for normal protein glycosylation during this delay, we measured the glycogen content of 3T3-L1 adipocytes. From an initial value of 0.537 +/- 0.097 mumol glucose/10(6) cells, glycogen was depleted in a time-dependent manner in response to glucose deprivation, exhibiting a half-time of 6 h. Surprisingly, fructose did not prevent glycogen depletion. However, in such glycogen-depleted adipocytes, the alteration of GLUT-1 glycosylation in response to glucose deprivation was more rapid than in normal adipocytes. Chinese hamster ovary (CHO) cells, which synthesize abbreviated dolichol-linked oligosaccharides within minutes of glucose deprivation (J. I. Rearick, A. Chapman, and S. Kornfeld. J. Biol. Chem. 256: 6255-6261, 1981), contained only 1% of the level of glycogen found in 3T3-L1 adipocytes. Glycosylation of GLUT-1 was altered in CHO cells within 3 h of glucose deprivation. These data demonstrate that, during glucose stress, glycogen may serve as a buffer for oligosaccharide biosynthesis and provide a potential explanation for varying sensitivities of different cell types to glucose deprivation.

3T3 Cells↗