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Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 271 records · Page 15Linked to original sources
PubMed1994

Transgenic mice expressing human apoB100 and apoB48.

Transgenic mice that express human apolipoprotein (apo)B have been developed by microinjecting fertilized mouse oocytes with an 80 kb genomic DNA fragment that encompasses the entire human APOB gene. In the transgenic mice expressing the largest amounts of human apoB, the concentration of human apoB100 in the plasma is nearly as high as the levels observed in normolipidemic humans (50 mg/dl). Virtually all of the human apoB100 in the transgenic plasma is located in the LDL fraction, resulting in substantially increased levels of LDL cholesterol. These human apoB-transgenic mice should be useful animal models for understanding various aspects of lipoprotein metabolism and for further delineating the role of LDL in atherogenesis.

Animals↗
PubMed1994

Orthographic analogies and phonological awareness: their role and significance in early reading development.

Two studies investigated young children's use of analogies in reading. In Study 1, 6-year-old children were trained to criterion on a series of clue words. Following training, they read more words that shared spelling patterns with the clue words than control words. However, this effect was reduced when the clue word was not exposed at post-test. Study 2 showed that there was a significant relationship between rhyming and analogizing at age 6, but the predictive relationship between phonological skills at ages 4 and 5 and use of analogy at age 6 was not significant.

Awareness↗
PubMed1994

Neuropsychological deficits, caregivers' perception of deficits and caregiver burden.

OBJECTIVE: We tested three hypotheses about the effects of perceived and actual patient deficits on caregiver burden: (1) objective patient deficits directly influence caregiver burden; (2) caregiver burden is the result of caregiver perceptions of patient deficits; (3) objective patient deficits influence caregiver burden indirectly by determining perceived deficits. DESIGN: Causal modeling. SETTING: A hospital-based out-patient diagnostic clinic. PARTICIPANTS: An elderly sample (n = 136) referred to a diagnostic dementia clinic and their caregivers. MEASUREMENTS: Neuropsychological tests of patient functioning, a measure of patient mood (the Geriatric Depression Scale), caregiver perceptions of patient functioning, and a measure of caregiver burden (the Burden Interview). RESULTS: The Geriatric Depression Scale and neuropsychological battery-based indices of functioning were not predictive of caregiver burden. Caregiver perceptions of patient dysphoria, and of everyday functioning skills were related to burden. Caregiver perceptions of patient memory, self-care, and language skills were unrelated to caregiver burden. CONCLUSIONS: The results are consistent with the Lazarus and Folkman model of stress and coping; the caregiver's perceptions of the patient's functioning were the most important determinants of caregiver burden. Objective patient deficits influenced caregiver burden indirectly by influencing caregiver perceptions of patient deficits. These findings suggest that practitioners attempting to assess and manage caregiver burden should attend to the caregivers' perceptions of patient mood and everyday functioning. The relationship of caregiver appraisals with actual patient deficits also sheds light on the nature of caregiver stress.

Aged↗
PubMed1994

Stimulus estimation and the overprediction of fear.

Overprediction of fear is the tendency to overestimate the amount of fear that one will experience in a subjectively threatening situation. Little is known about this bias, despite the important role it appears to play in producing phobic avoidance. The present study proposed a stimulus estimation hypothesis of overprediction, which states that overprediction of fear arises from the overprediction of the danger features of the feared stimulus and the underprediction of safety features. This model was supported by the results of structural equation modelling based on the responses of 224 snake-fearful subjects exposed to a live harmless snake. The determinants of the stimulus estimation bias are considered and directions for further investigation are discussed.

Adult↗
PubMed1994

Sequences containing the second-intron enhancer are essential for transcription of the human apolipoprotein B gene in the livers of transgenic mice.

To identify DNA sequence elements from the human apolipoprotein B (apoB) gene required for high-level, correct tissue-specific expression in transgenic mice, we made several constructs that included one or more of the key regulatory elements that were previously characterized with cultured liver-derived and intestine-derived cell lines. Our data show that the apoB promoter alone (-898 to +121) is not sufficient to direct transcription in transgenic mice. An enhancer located in the second intron is absolutely required to specify transcription by the homologous apoB promoter in the livers of transgenic mice; this enhancer does not direct transcription in the small intestines. Thus, the elements controlling transcriptional activation of the apoB gene in the liver and the intestine in vivo are distinct and separable. Analysis of the DNase I hypersensitivity of the integrated human transgenes in various lines of expressing and nonexpressing mice suggests that the formation of DH4, a strong hypersensitive site in intron 2, may be a prerequisite for hepatic expression of the apoB gene. Nuclear matrix association regions (MARs) of the apoB gene may play a role in transgene expression. Constructs including MAR sequences displayed higher levels of expression than those lacking them. However, these MARs did not completely insulate the associated transgenes from position effects.

Animals↗
PubMed1994

Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification, and sustained expression of an exogenous gene in vivo.

To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.

Animals↗
PubMed1994

Somatosensory evoked fields and potentials following tibial nerve stimulation.

We studied evoked magnetic fields and electrical potentials following stimulation of the tibial nerve in a group of 24 normal subjects. Both magnetic and electrical recordings demonstrated a series of oscillatory patterns consisting of four peaks (two positive and two negative) occurring between 40 and 100 msec. Magnetic field source localization of all four peaks using a dipole-in-a-sphere model indicated that all four peaks emanated from the same cortical surface located within the longitudinal fissure, an area typically associated with somatosensory function.

Adult↗
PubMed1994

Cognitive impairment and medication adherence.

1. The findings of this study are congruent with previous work that found that subjects' knowledge about medication is not necessarily correlated with adherence to medication regimens. 2. The nature and experience of forgetting medications merits further investigation. Asking patients about forgetting medication is easy to do, and many methods of compensating for forgetfulness are available. 3. Cognitive impairment was not associated with medication adherence. Cognitively impaired elders were likely to have caregivers assisting in the administration of their medication in the period immediately after discharge from acute care facilities.

Aged↗
PubMed1994

Protein kinases share a common structural motif outside the conserved catalytic domain.

A comparison of the sequences of the mammalian and Dictyostelium catalytic subunits of cAMP-dependent protein kinase revealed extensive sequence similarities through the catalytic core and the carboxy terminal tail. The amino terminal sequences however differ dramatically. The large difference in size, 73 kDa for the Dictyostelium enzyme versus 40 kDa is due to an extension in the N-terminus. The mouse enzyme has at its amino-terminus a long amphipatic helix, the A-helix, that precedes the catalytic core, covering the surface of both lobes of the enzyme. Dictyostelium does in fact, have a similar motif but it is remote from the catalytic core, in the N-terminal extension. On the basis of molecular modeling, it is proposed that residues 77-98 correspond to a structural motif similar to the A-helix in mouse catalytic subunit. Sequences encoding similar putative motifs contiguous to the catalytic core can be recognized in many other protein kinases and is particularly prominent in all of the non-receptor tyrosine kinases. In the case of Src, this A-helix motif appears to serve as the linker between the conserved catalytic core and the SH2 domain. The interaction between the A-helix motif and the core is described, and the general occurrence of this structure within the protein kinase family is discussed.

Amino Acid Sequence↗
PubMed1994

Wound infection in total joint arthroplasty: effect of extended wound surveillance on wound infection rates.

OBJECTIVE: To determine the effects of a wound monitoring program on infection rates after total joint arthroplasty. DESIGN: Case series, comparing postoperative wound infection rates before and after hospital discharge. SETTING: A university-affiliated tertiary-care hospital. PATIENTS: A group of 865 patients who underwent primary or revision total hip or knee arthroplasty between September 1989 and September 1991 followed by in-hospital and post-discharge wound monitoring was compared with a baseline group of 204 patients who had undergone an arthroplasty procedure and in-hospital wound monitoring between March and September 1988; only 38 of these patients were selected for post-discharge monitoring. INTERVENTIONS: In the study group, wounds were monitored every 48 to 72 hours to the time of patient discharge and at 30 days post-discharge. Monthly reports of surgeon-specific and overall infection rates were sent to each surgeon during both baseline and study periods. MAIN OUTCOME MEASURES: Presence or absence of surgical wound infection. RESULTS: The initial overall wound infection rate was 9.9%. This decreased to 3.8% in the study group, after the wound monitoring program had been in place for at least 18 months. Post-discharge monitoring accounted for the majority of wound infections diagnosed. CONCLUSIONS: A wound monitoring program may be an important tool in lowering wound infection rates associated with total joint arthroplasty. Post-discharge monitoring is important in determining true wound infection rates.

Alberta↗
PubMed1993

Antibodies to the extracellular receptor domain restore the hormone-insensitive kinase and conformation of the mutant insulin receptor valine 382.

A mutation substituting a valine for phenylalanine at residue 382 in the insulin receptor alpha-subunit has been found in two sisters with a genetic form of extreme insulin resistance. This receptor mutation impairs the ability of the hormone to activate autophosphorylation of solubilized receptors and phosphorylation of substrates (Accili, D., Mosthaf, L., Ullrich, A., and Taylor, S. I. (1991) J. Biol. Chem. 266, 434-439). We have previously demonstrated that in native receptors insulin induces a conformational change in the receptor beta-subunit, which is thought to be necessary for receptor activation (Baron, V., Gautier, N., Komoriya, A., Hainaut, P., Scimeca, J. C., Mervic, M., Lavielle, S., Dolais-Kitabgi, J., and Van Obberghen, E. (1990) Biochemistry 29, 4634-4641). Hence, it was thought that a defect in this conformational change might explain the functional defect of the mutant receptor. This appears to be the case, as we demonstrate here that the mutant receptor is locked in its inactive configuration. However, we found two monoclonal antibodies, directed to the extracellular domain, which are capable of restoring the mutant receptor kinase activity. The activation of the mutant receptor was accompanied by restoration of conformational changes in the beta-subunit C terminus. From these data, we draw the two following conclusions. (i) A causal link exists between receptor kinase activation and the occurrence of conformational changes. (ii) Ligands other than insulin, such as antibodies, which perturb the extracellular domain, can function as alternative ways to restore the mutant receptor kinase.

3T3 Cells↗
PubMed1993

Motor neuron degeneration of mice is a model of neuronal ceroid lipofuscinosis (Batten's disease).

Pathological studies of mice homozygous for the motor neuron degeneration (Mnd) mutation show abnormalities similar to those of the human neuronal ceroid lipofuscinoses: sudanophilic, autofluorescent intraneuronal inclusions that are immunoreactive with antibodies to subunit c of mitochondrial ATP synthase. Ultrastructurally, the inclusions have the pentalaminar structure characteristic of some form of human neuronal ceroid lipofuscinosis and of canine and ovine models of neuronal ceroid lipofuscinosis. Similar inclusions are observed in many somatic organs and in the retina, which develops photoreceptor degeneration. This mutation, previously considered a model of amyotrophic lateral sclerosis, may be a useful model for molecular and genetic studies of human neuronal ceroid lipofuscinosis because mice have been well characterized genetically. Since they are inexpensive to breed and maintain, they can also be used to test therapeutic interventions.

Animals↗
PubMed1993

The structure of fundamental fears.

Reiss's expectancy theory states that panic attacks, phobias, and other fear reactions arise from three fundamental fears (sensitivities): anxiety sensitivity, fear of negative evaluation, and injury/illness sensitivity. The present study examined two central aspects of the theory: (1) the assumption that fundamental fears are factorially distinct, and (2) the proposition that fundamental fears account for variance in other forms of fear and in trait anxiety. Measures of fundamental fears, common fears, and trait anxiety were administered to 100 community volunteers. The results supported Reiss's theory; the fundamental fears were factorially distinct, minimally intercorrelated, and accounted for significant proportions of variance in measures of other fears and trait anxiety. Specific and conceptually meaningful links were found between fundamental fears and common fears.

Adult↗
PubMed1993

Outcome profiles in the treatment of unipolar depression.

Treatment efficacy is typically evaluated by examining group means and pre-post change scores. Although informative, such analyses may obscure individual or subgroup differences in response (outcome profiles). The present study used two different methods to define treatment outcome profiles--rationally-derived criteria (Frank et al., Archives of General Psychiatry 48, 851-855, 1991) and dynamic clustering--to evaluate four treatments of unipolar depression: behaviour therapy, amitriptyline, psychodynamic psychotherapy and relaxation training (attention placebo). The profiling methods yielded similar results. Regardless of treatment, the majority of patients displayed either a recovery or nonremission outcome profile, with relatively few instances of remission followed by a recurrence of depression. These findings challenge the view that any of the treatments are associated with a strong tendency to relapse, at least over the 3-month follow-up period. To further characterize the major outcome profiles, discriminant analysis was performed. Results indicated that recovery and nonremission profiles differed in that the latter was associated with a longer and more severe index episode and greater neuroticism. A number of variables, including family history of depression and therapists' prediction of outcome, failed to distinguish recovered from unremitted patients.

Adult↗
PubMed1993

Effects of cocaine on human aggression.

Thirty male undergraduates received either a placebo, low dose (1 mg/kg), or high dose (2 mg/kg) of orally administered cocaine. Subjects were then given the opportunity to administer electric shocks to an increasingly aggressive fictitious opponent during a competitive reaction-time task. Aggression was defined as the intensity of shock the subject was willing to set for his adversary. The results of this study indicate that subjects in the high-dose cocaine condition reacted more aggressively than placebo subjects irrespective of level of provocation.

Adolescent↗
PubMed1993

Kinetics of hydrolysis of cardiac S1 heavy chain isoforms and identification of light chain and actin binding sites.

OBJECTIVE: A comparative study of the kinetics of proteolysis of myosin S1 heavy chain was performed using dog ventricular and atrial S1 to distinguish between protease sensitive sites in S1 isotypes and to determine the binding sites on S1 heavy chain for LC1, LC2, and actin. METHODS: Digestion of S1 as a function of actin was performed at 25 degrees C at a trypsin to S1 ratio (w/w) of 1:1500. Myofibrils were digested (trypsin/myofibrils w/w ratio = 1:300) in the presence of ATP, ADP, and under rigor conditions. Light chain and actin binding sites were identified by the gel overlay method. RESULTS: Ventricular and atrial S1 were proteolysed at 0.13 min-1 and 0.04 min-1 respectively. Actin significantly reduced the cleavage rate of both S1 heavy chains by blocking hydrolysis at the 50/20 kD site. Myofibrillar myosin heavy chains from ventricles were also hydrolysed faster than those of the atria in the presence of 4 mM MgATP. The calculated rates were 0.42-0.50 and 0.17-0.19 min-1 for ventricular and atrial myofibrils respectively. MgADP 2 mM or absence of nucleotides reduced the cleavage rates to 0.04-0.07 (ventricular myofibrils) and 0.02-0.03 min-1 (atrial myofibrils) respectively. Gel overlay experiments showed that 125I labelled LC1 and LC2 bound to the 20 kD fragment and actin mainly to the 50 and 20 kD peptides. CONCLUSIONS: The 50/20 kD site in either ventricular or atrial S1 was blocked when actin was present, while proteolysis at the 25/50 site proceeded regardless of the presence of actin. However, the 25/50 site was less accessible to trypsin in the alpha myosin heavy chain, since the roughly threefold reduction in the rates of hydrolysis of atrial S1 heavy chain was also maintained in the myofibrils in rigor or in the presence of ADP. Although actin made contact with the 70 kD and the 25 kD fragments, the 50 kD and 20 kD fragments appeared to be the central "anchor" for binding of both light chains and actin.

Actins↗