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Biomedical subjects

D A Young

Publications and source records attributed to D A Young.

At least 55 records · Page 3Linked to original sources
PubMed1999

Sequence of apoptosis and inflammatory necrosis within the formative ovulatory site of sheep follicles.

The aim of this study was to define the temporal and spatial patterns of apoptosis, necrosis and inflammation within preovulatory ovine follicles. A gonadotrophin surge was induced in pro-oestrous ewes by GnRH, and isolated follicles were hemisected into apical and basal segments at 0, 10, 18 and 22 h (the time of ovulatory stigma development) after GnRH. Ovarian surface epithelial and granulosa cells were isolated and assessed by fluorescence microscopy for membrane phosphatidylserine translocation-annexin V (early-stage apoptosis), oligonucleosomal DNA nick endlabelling (advanced apoptosis), and nuclear propidium iodide incorporation (necrotic membrane disruption). Thecal shells were analysed for interstitial blood cells. Preovulatory follicles were also hemisected and subjected to electrophoretic DNA degradation analysis. Annexin V binding and in situ DNA fragmentation among ovarian surface epithelial and granulosa cells along the follicular apex were high 18 and 22 h after GnRH. Propidium iodide staining of apical ovarian surface and granulosa cells was apparent at 22 h. There was a coincident increase within the apical theca as the time of ovulation approached in extravasated leucocytes (18 and 22 h) and erythrocytes (22 h). Apoptotic DNA laddering and necrotic DNA smears within the follicular apex were evident on agarose gels at 18 and 22 h, respectively. In contrast, ovarian surface epithelium not associated with the ovulation site and the basal follicular wall were largely unafflicted. It is suggested that both modalities of cellular death, apoptosis and necrosis (with acute inflammation and vascular injury), contribute progressively to follicular stigma formation and ovarian rupture.

Animals↗
PubMed1999

Effect of feed intake on antimicrobially induced increases in porcine serum insulin-like growth factor I.

This study was conducted to determine whether an antimicrobially induced (ASP-250) increase in serum IGF-I was the result of differences in feed intake. Serum IGF-I concentrations were measured in crossbred pigs that were fed a control diet or a diet supplemented with ASP-250 either for ad libitum consumption or limited to 85% of the control pigs' consumption. The pigs that consumed either diet ad libitum, control or ASP-250, consumed similar quantities of feed. The ASP-250 ad libitum-intake pigs had serum IGF-I concentrations that were greater (P<.01) than those of their ad libitum-intake control littermates. Similarly, the ASP-250 limit-fed pigs had serum IGF-I concentrations that were greater (P<.01) than those of the controls. Although the serum IGF-I concentrations of pigs fed the ASP-250-supplemented diet for ad libitum intake were greater than the serum IGF-I concentrations of the pigs limit-fed the ASP-250-supplemented diet, the differences were not significant (P<.08). The ASP-250-fed pigs had higher serum IGF binding protein (BP)-3 concentrations than did their control littermates (P<.003). A time course of antimicrobially induced alterations in serum IGF-I concentrations revealed that the effect of increased serum IGF-I levels in ASP-250-supplemented pigs (P<.02) was observed within 4 d and was maintained throughout the 4-wk study. These findings show that feed intake is not responsible for the increase in serum IGF-I observed with ASP-250 supplementation. Additionally, the antimicrobially induced increase in serum IGF-I concentrations occurs within a few days after initiation of the treatment.

Animals↗
PubMed1999

Frontal lobe lesions and executive dysfunction in children.

OBJECTIVE: To investigate the relationship of frontal lobe lesions and neuropsychologic performance in school-aged children to determine whether damage to frontal regions results in specific cognitive sequelae. BACKGROUND: The role of the frontal lobes in executive function remains incompletely understood, particularly in children. METHOD: This retrospective study included children aged 8 to 17 with brain lesions of various etiology (n = 63) or diverse psychiatric disorders (n = 48). All were evaluated for details of neurologic and medical history and for scores on the Wechsler Intelligence Scale for Children (WISC-III) and the Wisconsin Card Sorting Test, and all but the psychiatric patients had neuroimaging scans. Five groups were analyzed--dorsolateral frontal, medial-orbital frontal, focal nonfrontal, diffuse, and psychiatric--and neuropsychologic test results were compared using a Kruskal-Wallis nonparametric analysis of variance. RESULTS: Children with damage to dorsolateral frontal regions were more impaired on the Wisconsin Card Sorting Test than those in all other groups. Comparable performance on the Wechsler scale was found in all groups, suggesting that intellectual functioning did not account for this difference. CONCLUSIONS: These data provide evidence for a prominent role of the dorsolateral frontal regions in the mediation of executive function in children. They also support the use of the Wisconsin Card Sorting Test in children as a measure of dorsolateral frontal integrity.

Adolescent↗
PubMed1998

Leukoregulin induction of protein expression in human orbital fibroblasts: evidence for anatomical site-restricted cytokine-target cell interactions.

The molecular basis for the profound inflammatory response and the accumulation of hyaluronan in orbital connective tissues seen in thyroid-associated ophthalmopathy is unknown. Moreover, the link between the orbital manifestations of Graves' disease and those in the pretibial skin, localized dermopathy, has yet to be established. We have reported recently that leukoregulin, an activated T lymphocyte-derived cytokine, dramatically induces hyaluronan synthesis and prostaglandin-endoperoxide H synthase 2 in human orbital fibroblasts in culture. In the current studies, utilizing giant two-dimensional gel electrophoresis, we find that orbital fibroblasts express constitutively a protein profile that distinguishes them from skin fibroblasts derived from the abdominal wall and from the pretibium. We further demonstrate that leukoregulin, when present in culture medium for 16 hr, up-regulates a set of orbital fibroblast proteins not present in untreated cultures or in fibroblasts from the abdominal wall. However, some of the same protein inductions are present in the pretibial fibroblasts. These leukoregulin-induced changes in protein expression are completely blocked by dexamethasone (10 nM). Our findings are the first to identify proteins that appear to be expressed and differentially regulated in an anatomical site-restricted manner in orbital and pretibial fibroblasts and seem to establish a molecular link between fibroblasts from the orbit and those in pretibial skin.

Binding Sites↗
PubMed1998

Parallel nature of hippocampal synaptic plasticity.

This study demonstrates that the mechanisms involved in the production of long-term potentiation (LTP) in the hippocampus appear to be independent of those which generate shorter-lasting plasticity, but that both processes are activated concurrently following an LTP-inducing stimulus. Adult male Sprague-Dawley rats were anesthetized using either pentobarbital or secobarbital to record extracellular field potentials from the hippocampal CA1 pyramidal cell layer in response to stimulation of commissural afferents. Plasticity was generated by the delivery of a five-pulse patterned stimulus train, consisting of one priming pulse followed 170 milliseconds later by a burst of four pulses at 200 Hz. While similar LTP was observed in both groups, short-term plasticity was absent in the secobarbital-anesthetized animals. This result suggests that different plasticity mechanisms in the hippocampus are activated in parallel by the triggering stimulus.

Animals↗
PubMed1998

Characterization of a gene encoding a single-subunit bacteriophage-type RNA polymerase from maize which is alternatively spliced.

Single-subunit RNA polymerases belonging to the T3/T7 bacteriophage family are thought to be common throughout eukaryotes. We report the isolation and characterization of a nucleus-encoded single-subunit RNA polymerase gene from maize. This gene is highly homologous to other single-subunit RNA polymerase genes from Arabidopsis, Chenopodium. yeast and Neurospora crassa involved in organellar transcription. Genomic Southern analysis reveals 10 to 15 hybridising fragments, suggesting that maize contains a small gene family. The isolated gene contains 19 exons and its genomic structure is highly conserved when compared to the three Arabidopsis homologues. Unlike the case in Arabidopsis, intron-12 of the maize bacteriophage-type RNA polymerase gene is alternatively spliced. Quantitative RT-PCR revealed that the resultant alternatively spliced transcript represents approximately 21 to 26% of the total polymerase mRNA in maize coleoptiles. The orthologous wheat bacteriophage-type RNA polymerase is also alternatively spliced and the intron exhibits 78% identity to maize intron-12. The conservation in alternative splicing between wheat and maize and its absence from Arabidopsis suggest a functional requirement for the alternatively spliced product.

Alternative Splicing↗
PubMed1998

Improvement in smooth pursuit eye movements after cigarette smoking in schizophrenic patients.

This study examined whether schizophrenics' cigarette smoking normalized smooth pursuit eye movement abnormalities. Fifteen schizophrenic and 15 nonschizophrenic subjects abstained from their usual cigarette smoking for an average of 10 h. Their baseline performance during a constant velocity smooth pursuit task was then assessed. The subjects smoked as much as they desired in a 10-min period and then were retested immediately postsmoking, and 10 and 20 min later. Smooth pursuit gain and the percentage of total eye movement due to various saccadic subtypes were computed using infrared oculography and computerized pattern recognition software. After smoking, smooth pursuit gain increased and the percentage of total eye movements due to leading saccades decreased significantly in the schizophrenic patients. There were no changes in the gain or leading saccades of nonschizophrenic subjects after smoking. Nicotinic receptor dysfunction may be a candidate mechanism for smooth pursuit eye movement abnormalities in schizophrenia.

Adult↗
PubMed1998

Further parameters of insight and neuropsychological deficit in schizophrenia and other chronic mental disease.

Evidence has begun to accumulate which suggests that lack of awareness of illness in schizophrenia is related to and possibly the result of a cognitive deficit involving prefrontal cerebral dysfunction. This study further explores this relationship along with other domains of self-awareness in chronic schizophrenics and other subjects with serious mental disorders. One hundred eight schizophrenics and 21 bipolar subjects from three separate sites in Britain, Germany, and Canada were administered the Wisconsin Card Sorting Test and three measures of self-awareness. Lack of illness awareness and other domains of self-knowledge were significantly more related to poorer neuropsychological performance in schizophrenia patients than in the other subjects. The results support the hypothesis that lack of illness awareness is related to defective frontal lobe functioning as indexed by neuropsychological measures.

Activities of Daily Living↗
PubMed1997

Increased levels of the nicotine metabolite cotinine in schizophrenic smokers compared to other smokers.

The purpose of this study was to determine if schizophrenic patients self-administer more nicotine during cigarette smoking than nonschizophrenic subjects. Urinary cotinine, a nicotine metabolite, was measured in 20 schizophrenic patients and 20 nonschizophrenic subjects with similar smoking history. Schizophrenic patients had significantly higher urinary cotinine levels, suggesting that schizophrenics consume higher doses of nicotine, probably by deeper inhalation of cigarettes. Schizophrenic patients' higher dose of nicotine may target different receptors than those activated by the lower doses self-administered by most nonschizophrenic smokers. In particular, high doses may activate low-affinity alpha-7 nicotinic receptors, associated with deficits in sensory inhibition in schizophrenia.

Adult↗
PubMed1997

Inducibility of E4BP4 suggests a novel mechanism of negative gene regulation by glucocorticoids.

The major biological effects of glucocorticoids are thought to be initiated through changes in the expression of cellular genes. However, the mechanisms involved in the suppression of some gene products by glucocorticoids are not well defined. ID13 mouse fibroblast cells were treated with the synthetic glucocorticoid dexamethasone (Dex) or with vehicle. Plus/ minus (+Dex/-Dex) cDNAs were used to screen an ID13 cDNA library. Using this method, we found that the recently identified human protein adenovirus E4 promoter binding protein (E4BP4) mRNA was induced by Dex in the ID13 cell line. E4BP4 is a transcriptional repressor and binds to a specific DNA element. Further investigation indentified E4BP4-like DNA elements located in the promoters of glucocorticoid repressed genes Cox-2, iNOS, and cPLA2. These findings suggest that E4BP4 may play a role in the glucocorticoid repression of these and other genes.

Adenoviridae↗
PubMed1997

Association of HSP60-like proteins with the L-system amino acid transporter.

The carrier protein(s) responsible for mammalian L-system amino acid transport has not been identified. Chronic lymphocytic leukemia (CLL) B-lymphocytes have markedly diminished L-system transport which is restored after treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Six candidate L-system related plasma membrane proteins were identified in TPA-treated CLL-cells using an L-system photoprobe and ultra-high-resolution two-dimensional gel electrophoresis. In the current studies, two candidate L-system related proteins were obtained from preparative giant two dimensional gels, and the amino acid sequences of peptide fragments from these proteins were determined by Edman degradation. These proteins, forming a doublet on the gels at an apparent size of 40 kDa and pI 5.85, had sequence homology to the mitochondrial heat shock protein 60 (hsp60). The presence of these proteins in CLL lymphocyte plasma membranes was confirmed by immunoblotting with antibodies to hsp60. These observations indicate that an hsp60 homologue is associated with the L-system amino acid transporter.

Amino Acid Sequence↗
PubMed1997

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness. Neurobiological investigations in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the alpha 7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness.

Auditory Perception↗
PubMed1997

Bovine papillomavirus E5 oncogene stimulates DNA synthesis in C127 fibroblasts without general effects on growth factor responsive protein phosphorylations.

The bovine papillomavirus (BPV) transforming gene E5 is thought to modulate growth factor receptor function leading to a stimulation of growth factor signal transduction pathways. However, the influence of E5 on the range of receptor mediated changes in protein phosphorylation has not been addressed. We looked for the influence of E5 on DNA synthesis as well as the phosphorylation of over 1000 cellular phosphoproteins in mouse C127 fibroblasts and subclones harboring wild type (ID13)-, E5- mutant (XL3-2), and E6- (E6oCl) mutant BPVs. The cells containing E5 had an altered growth response to fresh serum or PDGF but we observed no general influences of E5 transformation on sets of serum-, phorbol ester-, and PDGF-responsive phosphoproteins, comprising 25, 18, and 16 overlapping members, respectively. Indeed, most of the phosphoproteins comprising these sets remain equally responsive to these growth factors in all four cell lines. The only evidence of an E5-specific influence on protein phosphorylation was with 4 phosphoproteins, two whose PDGF-responsiveness was abolished and two with abolished serum-, phorbol ester- and PDGF-responsiveness. Thus E5 modulates only a subset of the cascade of receptor-mediated downstream protein phosphorylations.

Animals↗
PubMed1997

A cross sectional study of 100 athletes with jumper's knee managed conservatively and surgically. The Victorian Institute of Sport Tendon Study Group.

OBJECTIVES: Jumper's knee causes significant morbidity in athletes of all standards. However, there are few reference data on the clinical course of this condition in a large number of patients, and the aim of this study was to rectify this. METHODS: A retrospective study of the course of jumper's knee in 100 athletes who presented to a sports medicine clinic over a nine year period was carried out. Subjects completed a questionnaire designed to collect details of sport participation, symptoms, and time out of sport. Ultrasonographic results were recorded from the radiologists' reports. Histopathological results were obtained for patients who had surgery. RESULTS: Forty eight subjects recalled that symptoms of jumper's knee began before the age of 20 years. Symptoms prevented 33 from participating in sport for more than six months, and 18 of these were sidelined for more than 12 months. Forty nine of the subjects had two or more separate episodes of symptoms. Ultrasonography showed a characteristics hypoechoic region at the junction of the inferior pole of the patella and the deep surface of the patellar tendon. Histopathological examination showed separation and disruption of collagen fibres on polarisation light microscopy and an increase in mucoid ground substance consistent with damage of tendon collagen without inflammation. CONCLUSIONS: Jumper's knee has the potential to be a debilitating condition for a sports person. About 33% of athletes presenting to a sports medicine clinic with jumper's knee were unable to return to sport for more than six months.

Adolescent↗
PubMed1997

Fieller's theorem, Scheffé simultaneous confidence intervals, and ratios of parameters of linear and nonlinear mixed-effects models.

The issue of joint confidence region and simultaneous confidence interval estimation for ratios of the parameters of a nonlinear mixed-effects model is addressed using a Fieller's theorem approach. The method presented is similarly applicable to linear mixed-effects models. In addition, previous work on linear fixed-effects models is demonstrated to be a special case of the present method. The methodology is applied to the ratios of slopes in a study of gestational maturation of placental glucose transfer capacity in sheep.

Animals↗
PubMed1996

Leukoregulin induction of prostaglandin-endoperoxide H synthase-2 in human orbital fibroblasts. An in vitro model for connective tissue inflammation.

Several proinflammatory cytokines can increase prostaglandin E2 (PGE2) synthesis in a variety of cell types, constituting an important component of the inflammatory response. We demonstrate here that leukoregulin, a 50-kDa product of activated T lymphocytes, dramatically increases PGE2 synthesis in cultured human orbital fibroblasts. This up-regulation is mediated through an induction of prostaglandin-endoperoxide H synthase-2 (PGHS-2), the inflammatory cyclooxygenase. Steady-state levels of PGHS-2 mRNA are increased within 1.5 h of leukoregulin addition and are near maximal by 6 h, when they are 50-fold or higher above basal levels. The increase in PGHS-2 mRNA levels is partially blocked by cycloheximide, suggesting de novo synthesis of an intermediate protein may be required for a maximal leukoregulin response. Nuclear run-on studies indicate PGHS-2 gene transcription is up-regulated by leukoregulin 2-fold after 2 and 6 h. PGHS-2 protein, as assessed by Western blotting and two-dimensional protein gel analysis, is increased dramatically in orbital fibroblasts. This lymphokine-dependent expression of PGHS-2 is blocked by dexamethasone, and the increase in PGE2 and cAMP levels following leukoregulin treatment is also blocked by indomethacin and by SC 58125, a newly developed PGHS-2-selective cyclooxygenase inhibitor. The dramatic increase in cAMP levels causes marked alteration in orbital fibroblast morphology. PGHS-2 expression in dermal fibroblasts is also increased by leukoregulin; however, the response is considerably less robust, and these cells do not undergo a change in morphology. Both orbital and dermal fibroblasts express high levels of PGHS-1 mRNA and protein, the other abundant form of cyclooxygenase. In contrast to its effects on PGHS-2 expression, leukoregulin fails to alter PGHS-1 levels in either orbital or dermal fibroblasts, suggesting that PGHS-1 is not involved in cytokine-dependent prostanoid production in human fibroblasts. The increased PGHS-2 expression elicited by leukoregulin in orbital fibroblasts may be a consequence of both transcriptional and post-transcriptional effects. These observations help clarify the pathogenic mechanism relevant to the intense inflammation associated with Graves' ophthalmopathy. Lymphocytes trafficked to orbital tissues have a putative role, through the cytokines they release, in the activation of fibroblasts in this autoimmune disease.

Blotting, Northern↗
PubMed1996

Cholinergic deafferentation enhances rat hippocampal pyramidal neuron responsiveness to locally applied nicotine.

We tested whether cholinergic denervation of the hippocampus of young rats would result in an enhancement of CA1 pyramidal cell responsiveness to nicotine. Electrolytic lesions of the medial septal area were performed in young male Fisher 344 rats. One month later the rats were anesthetized with pentobarbital and nicotine was locally applied to CA1 pyramidal neurons using pressure microejection. The dose of nicotine required to excite the pyramidal neurons was significantly lower for cells recorded from rats with septal lesions. However, no changes in hippocampal cytisine or alpha-bungarotoxin binding were found.

Alkaloids↗