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Biomedical subjects

K Ross

Publications and source records attributed to K Ross.

At least 55 records · Page 3Linked to original sources
PubMed1992

Localization of dopamine D2 receptor protein in rat brain using polyclonal antibody.

The precise distribution of the dopamine type D2 receptor has been mapped for the first time in rat brain using an antibody to D2 receptor protein. Polyclonal antisera were collected from rabbits inoculated with an undecapeptide identical to residues 24-34 of the D2 protein sequence. Rat brain slices, 40 microns in thickness, were incubated with either primary antiserum, the antiserum plus free peptide antigen, or pre-immune serum. Antibody binding was visualized by peroxidase-antiperoxidase (PAP) reaction followed by light microscopy. PAP complex bound moderately-to-densely throughout the medial forebrain bundle, and was seen in more discrete regions in the midbrain, consistent with the binding of D2 radioligands. There were some unexpected results, namely in the cerebral cortex and nucleus accumbens, there were unexpectedly steep gradients in binding density, decreasing caudally; no binding was detected in the hippocampus or the substantia nigra pars reticulata. In all positive-staining regions examined, the antibody was highly localized to neuronal cell bodies, except in the frontal cortex where antibody was also evident on basilar dendrites. These data confirm that the polyclonal antibody recognized dopamine D2 receptor protein throughout the rat brain, and suggest that the D2 receptor is distributed more abundantly on somata than on cellular processes.

Animals↗
PubMed1992

Transforming growth factor-alpha is a potential mediator of estrogen action in the mouse uterus.

To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGF alpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGF alpha mRNA in the mouse uterus in a dose- and time-dependent manner. The up-regulation of TGF alpha transcripts occurs predominantly in uterine epithelial cells. RIA and Western blot analysis demonstrate that immunoreactive TGF alpha protein is secreted at high levels into mouse uterine luminal fluid after estrogen treatment. The induction of uterine TGF alpha mRNA is specific to estrogen; nonestrogenic steroids did not induce expression. Antibody specific to TGF alpha significantly reduces estrogen-mediated uterine growth, which supports the concept that TGF alpha is a mitogen for the reproductive tract. Analysis of TGF alpha/EGF receptors by binding, affinity labeling, and phosphorylation studies indicates that functional receptors are present in the mouse uterus after estrogen exposure. Thus, our data support a physiological role for TGF alpha and its receptor pathway in the female mouse reproductive tract.

Animals↗
PubMed1991

Glucose analogue inhibitors of glycogen phosphorylase: the design of potential drugs for diabetes.

The T-state crystal structure of the glucose-phosphorylase b complex has been used as a model for the design of glucose analogue inhibitors that may be effective in the regulation of blood glucose levels. Modeling studies indicated room for additional atoms attached at the C1-beta position of glucose and some scope for additional atoms at the C1-alpha position. Kinetic parameters were determined for alpha-D-glucose: Ki = 1.7 mM, Hill coefficient n = 1.5, and alpha (synergism with caffeine) = 0.2. For beta-D-glucose, Ki = 7.4 mM, n = 1.5, and alpha = 0.4. More than 20 glucose analogues have been synthesized and tested in kinetic experiments. Most were less effective inhibitors than glucose itself and the best inhibitor was alpha-hydroxymethyl-1-deoxy-D-glucose (Ki = 1.5 mM, n = 1.3, alpha = 0.4). The binding of 14 glucose analogues to glycogen phosphorylase b in the crystal has been studied at 2.4-A resolution and the structure have been refined to crystallographic R values of less than 0.20. The kinetic and crystallographic studies have been combined to provide rationalizations for the apparent affinities of glucose and the analogues. The results show the discrimination against beta-D-glucose in favor of alpha-D-glucose is achieved by an additional hydrogen bond made in the alpha-glucose complex through water to a protein group and an unfavorable environment for a polar group in the beta pocket. The compound alpha-hydroxymethyl-1-deoxy-D-glucose has an affinity similar to that of glucose and makes a direct hydrogen bond to a protein group. Comparison of analogues with substituent atoms that have flexible geometry (e.g., 1-hydroxyethyl beta-D-glucoside) with those whose substituent atoms are more rigid (e.g., beta-azidomethyl-1-deoxyglucose or beta-cyanomethyl-1-deoxyglucose) indicates that although all three compounds make similar polar interactions with the enzyme, those with more rigid substituent groups are better inhibitors. In another example, alpha-azidomethyl-1-deoxyglucose was a poor inhibitor. In the crystal structure the compound made several favorable interactions with the enzyme but bound in an unfavorable conformation, thus providing an explanation for its poor inhibition. Attempts to utilize a contact to a buried aspartate group were partially successful for a number of compounds (beta-aminoethyl, beta-mesylate, and beta-azidomethyl analogues). The beta pocket was shown to bind gentiobiose (6-O-beta-D-glucopyranosyl-D-glucose), indicating scope for binding of larger side groups for future studies.

Deoxyglucose↗
PubMed1991

Liver-specific gene expression: A-activator-binding site, a promoter module present in vitellogenin and acute-phase genes.

The A2 vitellogenin gene of Xenopus laevis, which is expressed liver specifically, contains an A-activator-binding site (AABS) that mediates high in vitro transcriptional activity in rat liver nuclear extracts. Footprint experiments with DNase I and gel retardation assays revealed the binding of several proteins to AABS. Using binding sites of known DNA-binding proteins as competitors in the gel retardation assay, we found that the transcription factor C/EBP and/or one of its "iso-binders" as well as LFB1/HNF1 bound AABS. These interactions were confirmed by in vitro transcription experiments using various oligonucleotides as competitors. However, saturating amounts of C/EBP- and LFB1/HNF1-binding sites as competitors only partially blocked AABS-mediated transcriptional activity. This finding implies that at least a third distinct transcription factor interacts with AABS. In vitro transcription experiments revealed that AABS was present not only in the closely related Xenopus A1 vitellogenin gene but also in acute-phase genes as a liver-specific regulatory element known to confer the interleukin-6 response. Both AABS and the interleukin-6 response element are promoter modules interacting with at least three distinct transcription factors, including C/EBP and LFB1/HNF1.

Acute-Phase Proteins↗
PubMed1990

BAP, a rat liver protein that activates transcription through a promoter element with similarity to the USF/MLTF binding site.

The vitellogenin genes of Xenopus are liver-specifically expressed. An in vitro transcription system derived from rat liver nuclei allowed us to define the cis-element BABS (B-activator binding site) in the promoter of the B1 vitellogenin gene. An oligonucleotide encompassing the region from -53 to -44 linked to a TATA box is sufficient for a tenfold increase of the transcriptional activity. Gel retardation assays with nuclear rat liver proteins reveal two DNA-protein complexes: Complex 1 can be competed by the USF/MLTF binding site of the adeno major late promoter whereas complex 2 is a distinct protein we refer to as BAP (B-activator protein). In vitro transcription experiments in the presence of USF/MLTF binding site as competitor show that BAP is an efficient transcription factor. Based on UV cross-linking we estimate that BAP has a molecular weight of 58 kd. Phosphatase treatment reveals that DNA binding of BAP requires phosphorylation. BABS is also present in the hepatitis B virus enhancer suggesting that it might play a role in the tumorigenic potential of the virus.

Animals↗
PubMed1990

Computer assisted instruction for autistic children.

Since the beginning of 1980, Computer-Assisted-Instruction (CAI) has been used systematically in special education. The use of computers in the treatment of autistic children is highly controversial and emotional among parents and professionals. Fears of reinforcing autistic withdrawal are often mixed with insecurity and dislike of new technologies. On the other hand, positive effects of CAI on learning and behaviour are reported by parents and published as single case studies. The following paper relates perception, motivation, communication and behaviour--characteristics of autistic children to features of computer-assisted learning. Preliminary findings support the benefit of the use of computer-technology for the management of behaviour and learning of autistic children. In 12 autistics, video-taped evaluations showed higher enthusiasm ratings in computer-sessions than personal instruction sessions. Single case-studies demonstrated a positive influence of CAI on autistic children's behaviour-problems (e.g. avoidance of eye contact, echolalia) as well as improved spontaneous communication and better learning of academics.

Adolescent↗
PubMed1988

A cell-specific activator in the Xenopus A2 vitellogenin gene: promoter elements functioning with rat liver nuclear extracts.

Transfection experiments using Xenopus vitellogenin A2 gene constructs allowed us to identify an activator which increases the activity of the thymidine kinase promoter. The activator is located between -121 and -87 of the A2 vitellogenin gene and is separated by a stretch of curved DNA from the estrogen-responsive DNA element at -331. The activator functions in a cell-specific manner, as it is active in human breast cancer cells (MCF-7) as well as hepatoma cells but not in fibroblasts or HeLa cells. The activator is composed of at least three elements: elements 1 and 2 which form a partial palindrome, function independently, but act synergistically when combined. Element 3 is not active on its own, but supports elements 1 and 2. A TATA box region derived from the Xenopus albumin gene is sufficient for the function of the activator. In vitro transcription experiments using rat liver nuclear extracts demonstrate that the activator interacts with transcription factors. These factors are distinct from those recognizing HP1, a regulatory element common to several genes specifically expressed in hepatocytes.

Animals↗
PubMed1988

On the evolution of the adaptation of Lophopyrum elongatum to growth in saline environments.

Most species of the genus Lophopyrum Löve (Agropyron Geartn.) grow in saline environments and are more tolerant of saline stress than the species of the related genus Triticum L. A 56-chromosome amphiploid from the cross Triticum aestivum cv. Chinese Spring x Lophopyrum elongatum exceeded Chinese Spring in salt tolerance, measured as plant dry-matter production and seed yield in solution cultures with 250 mM NaCl. Thus, the adaptation of Lophopyrum to saline environments is expressed in the wheat genetic background. None of the disomic additions or substitutions of L. elongatum chromosomes in Chinese Spring showed a similar level of saline stress tolerance, which indicates that the trait depends on the activity of genes on more than one chromosome. Comparisons of disomic additions, double monosomic additions from half-diallel crosses among disomic additions, and disomic substitutions of L. elongatum chromosomes in Chinese Spring with Chinese Spring indicated that the enhanced salt tolerance of the amphiploid is primarily controlled by genes with minor effects on three of the seven chromosomes, 3E, 4E, and 7E, interacting in a largely additive manner. The salt tolerance of L. elongatum additionally depends on several minor nonadditive gene interactions. It is concluded that the adaptation of L. elongatum to growth in saline environments evolved by accumulation of new alleles in a number of loci, each with a relatively small effect on salt tolerance. It is further inferred that most of these new alleles were codominant to the original alleles and were able to act independently in enhancing salt tolerance.

Journal Article↗
PubMed1987

Colonoscopic therapy of acute pseudoobstruction of the colon.

All patients with the diagnosis of acute colonic pseudoobstruction at the University of California, Davis Medical Center from 1979-1985 were reviewed. These 25 patients were initially treated conservatively (nasogastric tube/rectal tube/enemas) and this was successful in eight of 25 patients (32%). The remaining 17 patients (68%) unresponsive to conservative therapy received endoscopic intervention, either colonoscopic suction decompression (CSD) or colonic suction decompression with proximal colonic tube placement (CDT) for continuous decompression. Of the endoscopic procedures performed, 13/17 (76%) resulted in successful acute decompression. Recurrences occurred in 6/13 (45%) (3/7 in the colonoscopic suction decompression group and three of six in the colonic tube placement group). In the 10 failures, six further procedures were attempted, but only one was successful. These patients were then treated conservatively. There were no instances of colonic perforation. Acute pseudoobstruction in our experience is a benign entity that can be safely and successfully treated nonsurgically. Colonoscopic suction decompression is often initially successful but has a high frequency of recurrence. Newer techniques to prevent recurrence, i.e., colonic tube placement, are of potential benefit but presently have technical problems.

Acute Disease↗
PubMed1986

The Aberdeen Mark II single-photon-emission tomographic scanner: specification and some clinical applications.

The construction, operation and physical characteristics of a single-section multi-detector single-photon-emission scanner are described. The machine has 24 detectors arranged along the sides of a square. Movements and data collection are under the control of a series of distributed microprocessors. Both head and trunk tomograms can be produced. The spatial resolution at the collimator focus is 9 mm in the transverse plane, and the effective slice thickness is 14 mm. The volume sensitivity is 300 counts/s kBq ml with a 20 cm diameter cylindrical phantom filled with 99Tcm solution. The application of this machine to the examination of the brain, liver and heart has been found to be clinically useful.

Brain↗
PubMed1986

The human needs model of nursing.

Nurses in the United Kingdom spend much time attempting to fit British nursing practice into the theoretical framework of American nursing models. This is often a manipulative process in that it seeks to establish positive links with a care delivery system totally unlike our own. In the present paper the authors detail the process of establishing a new nursing model which integrates nursing curricula, education and practice to meet the needs of patients, staff and students within their own health district. An over-emphasis on lower levels of human need is common within nursing practice, which, although often blamed upon lack of human and financial resources, is also due to practitioners' misconceptions. The latter are invariably the result of a lack of an adequate or overt, practice orientated, conceptual framework. The Human Needs Model of Nursing adapts Maslow's concept of human needs to create such a conceptual framework for practice. It places equal emphasis on those patient problems which arise as the result of unmet needs at higher levels as well as those at lower levels, thereby acknowledging the holistic and dynamic nature of man.

Holistic Health↗
PubMed1986

Clinical studies of intestinal folate conjugases.

Clinical differences between the two human intestinal mucosal folate conjugases were assessed by measurement of their activities in normal individuals and in patients with chronic diarrhea of differing causes. Intracellular folate conjugase (ICFC) was 15-fold more active than brush border folate conjugase (BBFC) in jejunal mucosa from seven obese patients undergoing elective gastric bypass surgery. The activity of ICFC was similar among normal volunteers and patients with diarrhea of unknown origin (DUO), gluten-sensitive enteropathy (GSE), inflammatory bowel disease (IBD), and the short bowel syndrome (IBD-SBS). By contrast, BBFC, sucrase, and lactase were decreased significantly in GSE, and BBFC was increased in IBD-SBS. The activity of BBFC correlated with lactase and with sucrase in the normal subjects and in patients with DUO, whereas no correlations were found with the activity of ICFC in any group. Our clinical studies confirm that ICFC and BBFC are different enzymes. ICFC is not affected by intestinal disease, whereas the activity of jejunal BBFC, like that of other brush border enzymes, is decreased by mucosal injury and is also capable of adapting to distal small intestinal disease or surgical resection.

Adult↗