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Biomedical subjects

R Nelson

Publications and source records attributed to R Nelson.

At least 37 records · Page 2Linked to original sources

Cystic fibrosis: what do patients know, and what else would they like to know?

As the survival of patients with cystic fibrosis (CF) improves, it becomes increasingly important to address such issues as employment, reproduction, and quality of life in adulthood. In this study, 22 patients and 20 parents completed a questionnaire about the natural history, treatment and genetics of cystic fibrosis. Patients and parents knew as much as each other about the natural history of cystic fibrosis. Patients under 13 knew significantly less about the genetics and treatment. All found probability questions about heredity difficult. All the patients indicated that they would like further information on the future and how they would cope, through CF literature, organized patient groups and, in adolescence, would prefer to obtain information from medical staff rather than parents. Patients had received considerable information about the disease and its treatment from parents and clinical staff, but few had discussed the day to day problems of living with cystic fibrosis. This study has identified specific areas of ignorance in patients with cystic fibrosis, areas that need addressing in view of the improved survival associated with this disease.

Adolescent

Smokeless tobacco: current status and future directions.

Smokeless tobacco is addicting, can cause physical dependence, and is associated with many health risks. In spite of these concerns over its use, minimal research has been conducted to understand the effects from and factors associated with smokeless tobacco use. Additionally, relatively few studies have examined potentially effective treatments for the smokeless tobacco user. This paper reviews the existing literature in this area and considers future directions for research.

Adolescent

Association of less common cystic fibrosis mutations with a mild phenotype.

A majority of cystic fibrosis (CF) genes (70 to 75%) share a single mutation, but the remaining 25 to 30% of defects are accounted for by more than 20 different mutations. One of the less frequent mutations, G551D, has been identified in the CF genes of two sibs and one unrelated adult patient. The adult patient also has a second rare mutation, delta I507. All three subjects exhibit a less severe phenotype than that normally associated with CF. This supports a hypothesis that the common mutation (delta F508) is responsible for the severe form of the disorder, and the minority of patients with a milder form tend to have mutations at other sites in the CF gene.

Adolescent

Antigenic homology among gram-negative organisms isolated from cattle with clinical mastitis.

This study examined the degree of serologic homology among mastitis pathogens. Antibodies were raised against the Rc mutant, Escherichia coli O111:B4 (strain J5) and affinity purified against lipopolysaccharide derived from the Ra mutant, Salmonella typhimurium TV119. These antibodies reacted with a battery of unrelated Gram-negative bacteria in whole cell ELISA. Bacteria with strong cross-reactions included a heterologous, smooth E. coli, Salmonella dublin, S. typhimurium, Salmonella newport, and Pseudomonas aeruginosa. Recognition of Klebsiella pneumoniae and Bordetella bronchisepticum was observed, but reactions were weaker than with the other isolates. The reduced recognition of these isolates probably reflects a masking effect of the bacterial capsule and variations in lipopolysaccharide structure. The polyclonal antibody did not recognize a Gram-positive isolate, Staphylococcus aureus. These immunoglobulins were then tested using whole cell ELISA against a panel of bacteria recovered from the mammary glands of cattle with clinical mastitis. Marked reactivity was noted against a variety of Gram-negative pathogens. Gram-positive isolates had lower recognition by Gram-negative core antigen specific immunoglobulin. The results suggest immunization with rough mutant bacteria may have broad application in the prevention of coliform mastitis.

Animals

Family and peer issues among adolescents with spina bifida and cerebral palsy.

Increasingly, children with disabling conditions are surviving through childhood into adolescence and beyond. This places increased importance on understanding adolescent, family, and peer relationships, which are critical to healthy development among adolescents in general and to transitions to successful adulthood among youths with physical disabilities in particular. The purpose of this study was to identify the patterns of family and peer interactions. One hundred two youths with spina bifida and 60 adolescents with cerebral palsy between the ages of 12 and 22 completed written psychological measures as well as an in-depth structured interview. Approximately 90% of youths with spina bifida and cerebral palsy resided at home, of whom 80.4% and 72% lived with both parents. Almost without exception, parental relationships were defined as positive, with no difference of attitude noted toward the mother and father. Relationships with parents for teenagers with spina bifida were marked by high levels of dependence on parents for personal care such as bowel programs and, for both groups, low levels of responsibility at home and lack of discussion with parents about sexuality or menstruation. Although friends were viewed as very important by most respondents (approximately 83%), relationships were characterized by extremely limited out-of-school contacts, negligible participation with organized social activities, and a primary orientation toward sedentary activities. Finally, regarding heterosexual relationships, whereas 44.1% of respondents with spina bifida and 54.2% of respondents with cerebral palsy said their friends dated, only 14.7% and 28.3% of study participants indicated that they had ever been on a date and, even for those teenagers, heterosexual social contacts were infrequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The Second Canadian Conference on Multiple Sclerosis.

The epidemiology of multiple sclerosis (MS) and the planning and i interpretation of clinical therapeutic trials were the subjects of a symposium on MS held on June 13, 1989. Several speakers addressed whether MS is a genetic or an environmental disease. An environmental trigger would resolve the relatively low penetrance of the disease in susceptible individuals, although the alternative hypothesis that MS is a multigenic disease would also account for this observation. Clinical trials have to date failed to confirm the efficacy of any immunosuppressive or other agent in the management of progressive MS. Magnetic resonance imaging (MRI) appears to be highly sensitive for monitoring the activity of MS. Preliminary evidence suggests that MRI activity correlates with longitudinal clinical assessments of disability. Immunologic tests, while valuable in determining pathophysiology of MS, have not been strongly correlated with clinical outcome.

Humans

Binding properties of detergent-solubilized NCAM.

An assay has been designed for the identification of NCAM-binding proteins present in an NP-40 detergent extract of brain membranes. This method, which is capable of analyzing both heterophilic and homophilic interactions, uses species-specific antibodies against NCAM in combination with radioiodination, so that after unlabeled chicken and iodinated frog brain membrane proteins were allowed to interact, the chicken NCAM could be specifically isolated by immunoaffinity adsorption. The radiolabeled frog proteins coisolated with chicken NCAM were then characterized by one- and two-dimensional gel electrophoresis in combination with immunoblotting. The only detectable NCAM-binding proteins were identified as the 140- and 180-kD forms of NCAM. The presence and absence of polysialic acid on NCAM did not change the amount or nature of the frog proteins immunopurified under these conditions. As an alternative for detecting heterophilic ligands, a simplified immunoprecipitation method was employed using either iodine or sulfate radiolabels. Again under these conditions only NCAM was detected. These results are consistent with the hypothesis that the major binding protein for NCAM is NCAM itself, and suggest that differences in polysialic acid content do not directly alter the properties of NCAM's homophilic binding site.

Animals

Non-invasive assessment of intraluminal lipolysis using a 13CO2 breath test.

Techniques available for the study of lipase activity in the gut are unsatisfactory. Breath tests measuring labelled carbon dioxide (13CO2) may provide a useful means for this assessment. Six subjects with cystic fibrosis and pancreatic insufficiency and 10 controls received a test meal containing [13C] trioctanoin, and breath 13CO2 was measured using a dual inlet, dual detector isotope ratio mass spectrometer. Comparison of postprandial breath 13CO2 enrichment allowed complete separation between children with pancreatic insufficiency and controls. Administration of one capsule of pancreatic enzyme with the test meal resulted in an increase in 13CO2 production in all six patients, and four capsules produced a further increase in five of the six. Serial fat balance studies on four of the patients while receiving comparable doses of oral enzyme failed to demonstrate a progressive improvement in fat absorption. The [13C]trioctanoin breath test may prove a safe, non-invasive technique not only for the detection of pancreatic insufficiency, but also for the quantitative study of intraluminal lipolysis.

Breath Tests

Background-induced flicker enhancement in cat retinal horizontal cells. I. Temporal and spectral properties.

1. Dim backgrounds can enhance small-spot flicker responses of cat retinal horizontal cells by a factor of 2 or more. 2. Intracellular marking with horseradish peroxidase (HRP) reveals that this enhancement effect occurs in--but is not necessarily limited to--the cone-connected, A-type horizontal cell. 3. Flicker amplitudes decrease over a frequency range from 3 to 36 Hz of square-wave photic stimulation. There is little evidence of flicker-response enhancement at 3 Hz. Flicker-response enhancement is typically 2-6 times larger at 35 than at 6 Hz. 4. Inspection of flicker waveforms indicates both a scaling-up of response signals with backgrounds and a distortion composed of 2- to 5-ms-latency decrease, expressed primarily within a quick component of OFF-repolarization. 5. Flicker enhancement first increases as a function of background irradiance and then decreases. The increasing limb has the dynamic range and spectral sensitivity of cat rods (507-nm peak). Enhancement is maintained during rod after-effects. The decreasing limb of the background-versus-intensity function results from light adaptation of cat, long-wavelength (red) cones. 6. The flicker responses themselves peak spectrally at approximately 555 nm and reflect only the activity of cat long-wavelength (red) cones, without evidence of intermixing of other photoreceptor mechanisms. 7. Thus within the first synaptic layer of the cat visual system, rod signals interact with the flicker responses of red cones, both increasing cone-signal amplitudes and modifying cone-signal waveforms. 8. The results are closely analogous to "suppressive rod-cone interaction" (SRCI) as described in human psychophysics. 9. An outer-plexiform-layer circuit involving rods, horizontal cells and cones may mediate rod-induced enhancement of cone flicker. This being the case, notions of horizontal-cell feedback interactions with cones may have to be modified and extended. A specific feedback model is elaborated in the companion paper.

Animals

Background-induced flicker enhancement in cat retinal horizontal cells. II. Spatial properties.

1. Intracellular recordings have been made from cat retinal horizontal cells stimulated with flickering test spots. Dim backgrounds increase flicker amplitudes in response to small but not large test stimuli. 2. This background-induced flicker enhancement has been measured for different slit- and square-test stimulus widths and the results compared with two spatial models for the enhancement effect. 3. In the "dark test-region" model it is argued that rods within the test region are unresponsive to background stimuli because of prior saturation by the test stimulus. Background-evoked rod signals decay passively from regions outside the test stimulus through a syncytial network into the recording site, where they act on the cone-to-horizontal-cell synapse, increasing its gain. 4. In the "changing length-constant" model rod signals reduce the length constant of a syncytial network by uncoupling the cells within it. This causes an increased response to small but not large test stimuli. 5. Both models are analytically evaluated with the use of a conductive-sheet approximation to the syncytial network. Expressions are derived for network polarization [(V(0, 0)] as a function of stimulus size. The specific stimulus shapes considered are disks, rectangles, slits, and squares in both bright and dark varieties. From these expressions predictions of response enhancement as a function of stimulus size are made for both models. 6. The dark test-region model provides for an exponential decay of flicker enhancement as a function of slit width but a steeper-than-exponential decay with the width of squares, in close agreement with experimental data. 7. The changing length-constant model makes qualitatively similar predictions. Flicker enhancement declines nearly exponentially with slit width. For square-shaped test stimuli the predicted decline of flicker enhancement with size is somewhat shallower than either the dark test-region-model curve or the experimentally determined curve. 8. As recorded in the same set of cells and under the same set of stimulus conditions (with the use of both slit- and square-test stimuli), the mean length constant of the peak-to-peak flicker component in the horizontal-cell response is 168 +/- 18 (SE) microns with the background and 232 +/- 45 microns in the dark. The mean length constant for the background-induced flicker enhancement, as fit by dark test-region-model curves, is 186 +/- 22 microns (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Human vascular permeability factor. Isolation from U937 cells.

Human vascular permeability factor (hVPF) is a glycoprotein that promotes fluid and protein leakage from blood vessels. The function of hVPF is at present unknown, but the potent bioactivities of this protein suggest that it could act during inflammation, wound healing, and tumor angiogenesis. hVPF was purified from serum-free conditioned medium of the human histiocytic lymphoma cell line U937 as a disulfide-linked dimeric 40-kDa protein that promoted dermal blood vessel leakage in guinea pigs at a dose of 20 ng (3 x 10(-9) M) and promoted in vitro endothelial cell growth at concentrations as low as 50 PM. Multiple forms of hVPF with apparent pI values greater than 7.5 were resolved using pH gradient electrophoresis. Antibodies against guinea pig vascular permeability factor were found to cross-react with hVPF. The N-terminal amino acid sequence of hVPF was similar to, but not identical with, the N-terminal sequence of guinea pig vascular permeability factor.

Amino Acid Sequence

Cell-type-specific and site-specific N-glycosylation of type I and type II human tissue plasminogen activator.

Tissue plasminogen activator (t-PA) is an important initiator of fibrinolysis. The t-PA polypeptide has four potential N-glycosylation sites of which three are occupied in type I (Asn-117, -184, and -448) and two in type II (Asn-117 and -448). In an effort to elucidate the factors controlling the expression of N-linked oligosaccharides on this polypeptide, we have used a combination of sequential exoglycosidase digestion, methylation analysis, and controlled acetolysis to determine the oligosaccharide structures at each of the N-glycosylation sites of type I and type II t-PA when isolated from a human colon fibroblast cell strain and from a Bowes melanoma cell line. Our results suggest the following: (i) type I and type II t-PA are N-glycosylated in an identical way at Asn-117 and Asn-448, when isolated from the same cell line; (ii) Asn-117 is predominantly associated with oligomannose-type structures in all cases; (iii) Asn-184 and Asn-448 are predominantly associated with complex-type structures when t-PA is isolated from fibroblast cells, but with both complex- and oligomannose-type structures when isolated from melanoma cells; (iv) fibroblast cell derived t-PA is associated with both neutral and sialylated oligosaccharides, while melanoma cell derived t-PA is also associated with sulfated oligosaccharides, which are located exclusively at Asn-448 of type II t-PA; (v) no complex-type structures occur in common between t-PA from the two cell lines. These results indicate that the t-PA glycoprotein is secreted by each cell line as a set of glycoforms, each glycoform being unique with respect to the nature and disposition of oligosaccharides on a common polypeptide. Further, the two cell lines express no glycoform in common, despite expressing the same t-PA polypeptide. The implications of these results for both the control of oligosaccharide processing in different cell lines and the genetic engineering of mammalian glycoproteins are discussed.

Amino Acids