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Biomedical subjects

D A Young

Publications and source records attributed to D A Young.

At least 73 records · Page 4Linked to original sources
PubMed1996

Neuropsychological dysfunction in parents of schizophrenics.

Neuropsychological measures designed to examine aspects of attention, learning efficiency, and memory were investigated in 14 schizophrenic probands, their 28 parents, and 18 normal individuals. Probands performed at levels significantly below normals on measures of attention and of learning efficiency and performed below their parents on a subset of the same measures. Eight families had one parent with a personal or ancestral pedigree history consistent with schizophrenia; the other parent's personal and ancestral history was negative for schizophrenia. In these families, the probands were significantly different from the negative-history parents, but not the positive-history parents on an aggregate index of attention. Schizophrenics were significantly different from both the positive- and negative-history parents on an aggregate index of learning efficiency. These results extend previous findings of specific neuropsychological dysfunction in attention and learning in schizophrenics to show that some of the deficits are present in a subgroup of their parents, those who are likely carriers of genes conveying risk for schizophrenia. The data suggest that a heritable component of the neuropsychological deficit is a primary dysfunction in attention, and that a secondary or additional deficit in learning may be evident in family members who actually express the disorder of schizophrenia.

Adult↗
PubMed1996

Relative activities of retrovirally expressed murine prostaglandin synthase-1 and -2 depend on source of arachidonic acid.

We have developed derivatives of mouse embryonic fibroblasts (10T1/2) and Chinese hamster ovary (AS52) cells that stably express high levels of murine prostaglandin synthase-1 or -2 (PGHS-1 or -2). The cDNAs were transferred using retroviral vectors and the resulting G418-resistant clones were analyzed for prostaglandin E2 (PGE2) production. Specific expression was confirmed by Western and Northern analyses. Enzyme activities, protein, and message levels peaked 1 (10T1/2) or 2 (AS52) days after seeding but decreased as cells became density arrested. Upon subculturing, enzyme activities returned to their initial high levels. With 10 microM exogenous arachidonic acid (AA) as the substrate, PGHS-1 activities were approximately 3- to 5-fold higher than PGHS-2 activities. Conversely, when exogenous AA was left out of the medium and only endogenous AA was available as substrate, enzyme activities were lower; but PGHS-2 activities were 5-fold (10T1/2) or 1.5-fold (AS52) higher than PGHS-1 activities. Following phorbol ester treatment to stimulate endogenous AA release, PGHS-2 activities increased over time and by 6 hours, were 4-fold (10T1/2) or 2-fold (AS52) higher than PGHS-1 activities. However, when calcium ionophore A23187 was used to stimulate endogenous AA release, maximum PGHS activities occurred within 30 min of treatment; PGHS-1 activities were equal to (10T1/2) or 2-fold higher (AS52) than PGHS-2 activities. Because these cell lines allow us to measure specific PGHS activity in intact cells, we were able to demonstrate that the relative activities of the two PGHS isozymes depend on the source of AA (exogenous versus endogenous) or biochemical stimulus used to mobilize endogenous AA (A23187 versus phorbol ester). These data suggest that PGHS-1 and PGHS-2 preferentially utilize different pools of AA and may be modulated through different stimulus-initiated pathways.

Animals↗
PubMed1996

Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group.

PURPOSE: To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.

Adult↗
PubMed1996

Heritability of inhibitory gating of the P50 auditory-evoked potential in monozygotic and dizygotic twins.

Most normal subjects suppress the P50 evoked response to repeated auditory stimulus when paired stimuli are presented, 500 ms apart. The ratio of the amplitude of the response to the second stimulus to that of the first forms a quantitative measure of the activity of a central inhibitory sensory gating mechanism. The variance of this measure in a group of monozygotic and dizygotic twin pairs was determined. The calculation of heritability (h2) indicates that a significant portion of the variance (0.44 or greater) is due to heritable factors. This study supports the use of the inhibitory gating of the P50 response as a phenotype for genetic studies of schizophrenia in which a P50 gating abnormality has been identified.

Acoustic Stimulation↗
PubMed1996

Muscle subcellular localization and recruitment by insulin of glucose transporters and Na+-K+-ATPase subunits in transgenic mice overexpressing the GLUT4 glucose transporter.

Insulin-stimulated glucose uptake in skeletal muscle is mediated through the GLUT4 glucose transporter. Transgenic (TG) mice overexpressing human GLUT4 in skeletal muscle show an increased ability to handle a glucose load. Here, the participation of the overexpressed GLUT4 in the response to insulin was examined. In TG mouse muscle, the GLUT4 protein content was 10-fold higher in crude membrane (CM), sevenfold higher in internal membrane (IM), and 15-fold higher in a plasma membrane (PM)-rich fraction, relative to non-TG littermates. This suggested partial saturation of the normal sorting mechanisms. The distribution and abundance of the GLUT1 glucose transporter was not affected. Insulin injection (4.3 U/kg body wt) increased GLUT4 in the PM-rich fraction; the increase was threefold higher in TG than in non-TG mice. Insulin decreased the GLUT4 content of the IM in both animal groups and of a second, heavier intracellular membrane fraction only in TG mice. The net content of Na+-K+-pump subunits was 40-65% lower in CM from TG compared with non-TG littermates. In spite of this, insulin caused a three- to sixfold higher translocation of the alpha2 and beta1 subunits of the Na+-K+-pump in TG compared with non-TG animals. The results suggest that overexpression of GLUT4 confers to the muscle increased ability to translocate subunits of the Na+-K+-pump either as a direct consequence of the recruitment of glucose transporters or as an adaptation to the more demanding metabolic state.

Animals↗
PubMed1996

Use of a mirror needle holder with transsclerally sutured posterior chamber intraocular lenses.

A mirror needle holder has been designed to facilitate the passage of a needle through the ciliary sulcus during transscleral fixation of posterior chamber (PC) intraocular lens (IOLs). Two human postmortem eyes were used to demonstrate the efficacy of this mirror used as the needle holder. This method was compared with the current method of passing sutures without view of the ciliary sulcus. The mirror needle holder demonstrated precise passage of the needle into the ciliary sulcus by direct visualization of the ciliary processes and sulcus. This method may avoid the complications associated with transsclerally sutured PC IOLs during penetrating keratoplasty and secondary IOL placement.

Ciliary Body↗
PubMed1995

Scaffolded instruction and the remediation of Wisconsin Card Sorting Test deficits in chronic schizophrenia.

The purpose of this study was to explore the remediation of Wisconsin Card Sorting Test (WCST) deficits among highly chronic schizophrenic patients by employing an instructional technique known as scaffolding. The extent to which learning of the WCST generalized to a similar neuropsychological test, the Short Category Test (SCT) was examined. Forty-one chronic schizophrenic subjects drawn from in-patient and out-patient wards were given the WCST. Twenty-eight of the subjects who displayed the greatest impairment on the WCST were then administered the Brief Psychiatric Rating Scale (BPRS) and randomly assigned to groups that received three sessions of either scaffolded or didactic instruction. Post-testing with the WCST occurred an average of 1.9 (SD = 1.3) and again 31.4 (SD = 3.9) days after instruction. Subjects who received scaffolded instruction improved significantly in the number of categories achieved when compared to the didactic group. The improvement was sustained a month later. A strong trend favoring the scaffolded group on the SCT suggested that generalization of learning had occurred. Significant and durable improvement of WCST performance in severely disabled schizophrenics is clearly possible with the instructional method employed. The increment in abstract reasoning may generalize to other tasks. These findings have significant implications for psycho-social and cognitive rehabilitation.

Adult↗
PubMed1995

Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude.

High-altitude residence during pregnancy is associated with an increased incidence of preeclampsia. To determine whether uteroplacental blood flow was reduced and pelvic blood flow distribution altered before the onset of hypertension, we measured common iliac (CI), uterine (UA), and external iliac (EI) artery flow velocities (FV), indexes of flow distribution, and blood volume (BV) at week 12, 24, and 36 of pregnancy and 6 mo postpartum in 23 normotensive, 7 preeclamptic, 5 transiently hypertensive, and 3 chronically hypertensive residents of 3,100 m. Normotensive women had a progressive increase in CIFV and UAFV, decrease in EIFV, redistribution of CIFV from the EI to the UA, and increase in BV with advancing pregnancy. Preeclamptic women attained maximal UAFV and redistribution of CIFV from the EI to the UA well before the onset of hypertension and, unlike normotensive women, showed no further increases near term. Plasma volume increment with pregnancy related to the fall in the EIFV/CIFV ratio. Transiently hypertensive women resembled normotensive subjects in the parameters measured, whereas chronically hypertensive subjects resembled preeclamptic subjects. We concluded that preeclamptic vs. normotensive pregnant residents of high altitude had less redistribution of CI flow to the UA and no increase in UA blood flow near term. That these differences were present before the onset of hypertension supports the concept that preeclampsia is characterized by an incomplete vascular adjustment to pregnancy.

Adult↗
PubMed1995

Treatment outcome of major fractures of the talus.

Twenty-six patients with major fractures of the talus were studied to assess the long-term outcome. The patients were admitted to a university teaching hospital and major trauma center from 1983 to 1991. The study excluded isolated fractures of the talar dome and posterior tubercle. Fifteen patients were treated using internal fixation and 11 patients were treated using nonsurgical methods. Avascular necrosis was detected in only four of the 26 patients. Subtalar osteoarthritis was a significant problem in 61%. Seven of these patients have come to secondary fusion procedures, with another three contemplating fusion procedures at the time of review. Only one patient developed significant avascular necrosis requiring a fusion procedure. Only three of 26 patients had not returned to work at a mean 6 years after their injury. Eleven of the 26 (42%) had not returned to their premorbid activity level. The majority of these patients (25/26) had sustained multiple injuries, which compromised the functional recovery from the talar injury. Early accurate diagnosis and anatomical reduction gave the best results. The low incidence of avascular necrosis in this study has been attributed to early anatomical stabilization of the fracture. We believe an early CT scan can more accurately assess the severity of the talar fracture and offers the best information for an appropriate treatment plan.

Adult↗
PubMed1995

Effects of reduced exposure on computed radiography: comparison of nodule detection accuracy with conventional and asymmetric screen-film radiographs of a chest phantom.

OBJECTIVE: Radiographic exposure has been thought to have little impact on the diagnostic quality of chest computed radiography because of automatic digital control of global optical density. The objectives of this study were to compare images obtained with two different exposures in computed radiography with conventional and asymmetric screen-film images of the chest for the detection of simulated lung nodules by use of receiver operating characteristic analysis and to relate differences in observer performance to parameters of image noise measured for each receptor condition. MATERIALS AND METHODS: At 110 kVp (fixed), exposures for the two screen-film systems were those necessary to achieve adequate optical densities over the lung and mediastinal regions of an anthropomorphic phantom. The two exposures used for the computed radiographs corresponded to the exposure used for the conventional chest screen-film system and an exposure 22% lower. An anthropomorphic phantom constructed of materials matched to the muscle, lung, and bone attenuation of a muscular adult man was used. Soft-tissue-equivalent plastic nodules of various sizes were secured at multiple sites on the phantom to simulate lung nodules. The chest phantom was imaged in 50 configurations with a total of 70 superimposed nodules. The perceptual performances of five radiologists were compared by use of receiver operating characteristic analysis. The signal-to-noise ratio in the mediastinum and the coefficient of variation of noise were measured for all four image conditions by use of a step wedge technique to provide an explanation for differences in diagnostic accuracy. RESULTS: We found no significant differences in the detection of lung nodules between the two screen-film systems or between the conventional screen-film images and the standard-exposure computed radiographs. However, there was a significant decrease in nodule detection on computed radiographs obtained at a reduced exposure; this result was associated with a 21% decrease in the signal-to-noise ratio. CONCLUSION: Our results show that underexposure of computed radiographs decreases the detection of low-contrast objects such as lung nodules. Although consistent global optical density on computed radiographs is achieved over a wide range of exposures, the alterations in signal-to-noise ratio that result from underexposure can reduce the diagnostic quality of computed radiographs.

Adult↗
PubMed1995

Pulmonary thromboembolism: spectrum of findings on CT.

CT has emerged as a potentially important diagnostic technique in pulmonary thromboembolism that can provide direct visualization of the obstructing embolus and its associated vascular and pleuroparenchymal sequelae. Although the role of contrast-enhanced CT in the diagnostic algorithm of pulmonary embolism has not been defined, patients at risk for pulmonary embolism frequently undergo thoracic CT as part of the assessment for other cardiopulmonary conditions. As such, CT may provide the first indication of clinically significant pulmonary embolic disease. This essay reviews the vascular, pleural, and parenchymal features of pulmonary thromboembolism observed on CT scans, describes the limitations of CT, and discusses the imaging features of pulmonary embolism that overlap other clinical conditions.

Adult↗
PubMed1994

In vitro studies of glucocorticoid effects on neurons and astrocytes.

Studies using immunocytochemistry and RNase protection assay demonstrate that glucocorticoid and mineralocorticoid receptors (GR, MR) and their corresponding mRNAs are co-expressed in hippocampal neurons cultured in serum-free, defined medium and at lower levels in cultured astrocytes. Addition of serum or medium conditioned by astrocytes increases the levels of MR mRNA, but has little effect on the levels of GR mRNA. Cellular levels of both GR mRNA and MR mRNA are upregulated by growth of embryonic hippocampal neurons in corticosterone. This is in distinct contrast to regulation of receptor expression in vivo where mRNAs for these receptors are downregulated in the rat hippocampus by corticosterone treatment of the adult adrenalectomized rat. However, in cultured astrocytes, GR and MR mRNAs are also downregulated by corticosterone. To begin to define the role of glucocorticoids in gene expression in astrocytes, we have used giant two-dimensional (2D) gel electrophoresis to separate astrocyte cellular proteins and translation products synthesized in vitro from astrocyte poly A+ RNA. Analysis of approximately 1,500 in vitro translation products by giant 2D gel electrophoresis reveals 11 protein inductions and 1 repression that occur at the level of mRNA in the absence of protein synthesis following treatment of astrocytes with corticosterone. Interestingly, these changes appear to be mediated by GR, but not by MR. The in vitro studies described here are relevant to identifying the role of GR and MR in gene expression in specific cell types in the hippocampus.

Animals↗
PubMed1994

Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo.

Prostaglandins are synthesized from arachidonic acid by the rate-limiting enzyme cyclooxygenase (prostaglandin G/H synthase). Active cyclooxygenase is encoded by two distinct and independently regulated genes, termed cyclooxygenase-1 (cox1) and cyclooxygenase-2 (cox2). In this investigation, we examined the expression of cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in vitro. Two h after BDE, rat aortic cox2 mRNA levels increased greater than 50-fold relative to the lowest detectable levels on days 2 and 14. No message was detectable in non-BDE control rat aortas. Similar to the results found in vivo, cultured SMC exhibited a greater than 45-fold increase in cox2 mRNA levels after a 2-h exposure to serum. This increase was transient because cox2 levels declined at 4 and 8 h. In contrast, minimal changes in cox1 mRNA levels were observed after BDE or serum treatments. Increased levels of cox2 mRNA and corresponding protein synthesis led to an accumulation of total cyclooxygenase protein, which remained elevated 24 h after serum stimulation. Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media. This increase is associated with a 2.5-3.0-fold increased rate of arachidonic acid conversion to prostaglandin E2. Our data indicate that injury and serum stimulation differentially regulate mRNA and protein expression of two distinct cox genes in vascular SMC in vivo and in vitro. The findings suggest that the prostanoid responses after vascular injury are, in part, mediated by acute increases in cox2 mRNA and cyclooxygenase-2 protein.

Animals↗
PubMed1994

Insulin action on whole body glucose utilization and on muscle glucose transporter translocation in mice.

Murine models of insulin resistance and diabetes are versatile and have been used to investigate genetic and metabolic disorders. However, the principal assays to assess insulin action, i.e., the euglycemic-hyperinsulinemic clamp and subcellular distribution of glucose transporters, have not been implemented in this species. Here we describe procedures which allow these methods to be adapted to mice. When normal C57bl/6j mice were infused with graded doses of insulin (1, 3, 10 or 30 mU/kg/min) during a euglycemic-hyerinsulinemic clamp, the glucose infusion rate necessary to maintain euglycemia increased in a dose-dependent manner (7.4 +/- 1.7, 13.1 +/- 3.6, 24.1 +/- 2.3 or 34.8 +/- 7.5 mg/kg/min), respectively. Hindlimb muscles were isolated and samples of 2-3 g were subjected to subcellular fractionation finalizing on 25%, 30% and 35% sucrose gradients. Fraction F25 (plasma membranes) was enriched in alpha 2 Na+/K(+)-ATPase and GLUT1 glucose transporters, whereas fraction F35 (intracellular membranes) was enriched in Ca(2+)-ATPase and GLUT4 glucose transporters. Following insulin treatment, GLUT4 increased in F25 and decreased in F35. Insulin treatment had no effect on GLUT1 in F25. However, unlike in rat skeletal muscle, GLUT1 was detectable in F35 and its content decreased in this fraction following insulin treatment. The results demonstrate that whole-body glucose utilization can be assessed in mice using euglycemic-hyperinsulinemic clamps and demonstrate how subcellular fractionation procedures can be applied to murine muscle. Murine muscle GLUT4 translocates from an intracellular storage site to the plasma membrane in response to insulin.

Animals↗
PubMed1994

Expression of human GLUT4 in mice results in increased insulin action.

Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32% and 56% reduction in serum glucose and insulin and a 69% and 33% increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stimulated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin-stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating whole-body glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state.

Adipocytes↗
PubMed1994

Saccadic eye movements in normal children from 8 to 15 years of age: a developmental study of visuospatial attention.

This cross-sectional study used saccadic eye movements, as measured by infrared occulography, to assess several aspects of visuospatial attention in normal children ages 8-15 years. Saccadic latency (a global measure of the ability to shift visuospatial attention), the ability to suppress extraneous saccades during fixation, and the ability to inhibit task-provoked anticipatory saccades all improve with age. However, the pattern of development differs for different tasks; saccadic latency shortens at a linear rate across the age range 8-15 years, while the capacity to inhibit anticipatory saccades matures by 12-13 years of age, and the ability to suppress saccades matures by 10 years of age. Analyses of age-related changes in oculomotor measures of attention may provide a novel approach in the study of children with attentional difficulties.

Adolescent↗
PubMed1994

Corticosterone-responsive mRNAs in primary rat astrocytes.

Glucocorticoids are important in neuronal development, regulation of the hypothalamic-pituitary-adrenal axis, adaptive behavior, and neuronal survival. Glia have receptors for glucocorticoid hormones and thus represent targets for hormone action in the brain. To identify mRNAs that are regulated by corticosterone in primary type 1 rat astrocytes, we have utilized ultra-high resolution giant two-dimensional gel electrophoresis of in vitro translated proteins. Our results reveal 12 in vitro translation products likely representing 10 mRNA species that are regulated by corticosterone. Eleven products are significantly increased and one decreased, most within 3 h of hormone treatment. Inclusion of cycloheximide does not prevent these changes, suggesting that they represent alterations in transcription; however, other mechanisms, such as changes in mRNA stability, cannot be excluded. Two corticosterone-regulated proteins were identified as glucocortin and glutamine synthetase. These two proteins are glucocorticoid-regulated in a variety of cell types, whereas the others appear to be astrocyte-specific. Future identification of these hormone-responsive mRNAs and proteins will help elucidate the molecular basis for glucocorticoid action in the CNS.

Animals↗