Biomedical subjects

P Norton

Publications and source records attributed to P Norton.

16 recordsLinked to original sources

PubMed1992

Cardiac dilatation associated with collagen alterations.

There is a complex collagen network in the heart. Various components have been identified and generally on the basis of form and position some functions have been ascribed to one or another of these components. Since the various components all appear to be connected in a hierarchial network of some type assigning function is not difficult but demonstrating a given function is somewhat hazardous. We have demonstrated that two I.V. infusions of disulfide reagents one week apart activates a collagenolytic system that results in near complete loss of the collagen struts that interconnect myocytes, the collagen struts that connect capillaries to all adjacent myocytes and the weave complex that surrounds groups of myocytes. Increases in pre load or afterload result in responses indicating that the disulfide treated animals generate pressure equal to or greater than the control hearts, thus, the treatment has no affect on either myocyte contractility or force delivery to the ventricle. However, static pressure volume measurements in the disulfide treated animals are shifted far to the right indicating marked dilatation of the ventricle and increase in distensibility. This indicates that the weave complex contributes to the initial rectilinear portion of the pressure volume curve.

Animals↗

PubMed1992

Computer system for the acquisition and analysis of vascular contractility. Application to a bioassay of endothelial cell function.

A system for the digital acquisition and subsequent analysis of the tension developed by isolated blood vessels in response to an endothelial cell superfusate is reported. Tension of the isolated rat aortic rings was measured by strain gauge. Strain-gauge output was then amplified, and the analog signal was digitized on a 16-channel A/D board. Lab tech Notebook software was used to display and store the data. The sampling rate was 0.1 Hz, and the data was written concurrently to hard disk and printer. Both disk and printer output were accompanied by a time stamp for subsequent ease of retrieval. The endothelial cell bioassay system allowed measurement of changes in vascular tension after the release of endothelium-dependent relaxing factor, nitric oxide (EDRF-NO) from cultured cells. Cells were cultured on microcarrier beads, formed into columns, and perfused with physiological salt solution. Significant (p < 0.05) relaxant responses occurred after agonist stimulation with bradykinin (10(-8) M; Emax -31.0% +/- 8.2%), acetylcholine (10(-8) M; Emax -33.2% +/- 5.0%), and calcium ionophore A 23187 (10(-6) M; Emax -55.7% +/- 15.4%). These responses were dependent on EDRF-NO, as shown by both the lack of relaxation in the absence of endothelial cells, and that relaxation to A 23187 was overcome by hemoglobin (3 x 10(-6) M). Results were manipulated graphically to allow the superimposition of data and thereby provide a mean and standard error of the mean for the entire time course of each response. Thus, a system was produced where fidelity of data expression was not dependent on measurements made at single points, but on the sampling frequency of the acquisition system.

Animals↗

PubMed1992

Light chain 2 profile and activity of human ventricular myosin during dilated cardiomyopathy. Identification of a causal agent for impaired myocardial function.

BACKGROUND: A number of parameters reflecting the effects of idiopathic dilated cardiomyopathy (IDC) on the structure and function of myosin from the human myocardium were analyzed. METHODS AND RESULTS: The content of the regulatory light chain, LC2, was reduced in myopathic heart myosin in contrast to the controls in which it was present in stoichiometric amounts relative to the essential light chain, LC1. In IDC hearts, the absence or significant reduction in amount of LC2 was related to the presence of an active protease, which was isolated and purified about 130-fold. The protease exhibited a significant degree of specificity: It cleaved LC2 almost totally (but not the heavy chains) in human control heart myosin but only partially cleaved LC2 in canine heart or in rabbit skeletal muscle myosins. The protease was present at a very low level or was inactive in control heart tissue. When the LC1/LC2 molar ratio was calculated, it was found to be 1:1.0 in control heart myosin and remained constant in various samples analyzed, whereas in myopathic myosin from different individuals, this ratio varied from 1:0.1 to 1:0.69. The rates of ATP binding to control and myopathic myosins were similar, whereas the Vm of actin-activated ATPase of myopathic myosin was about 25% less than that of the control. However, ATP binding and its hydrolysis by control S1, i.e., the myosin head, were faster by a factor of 2 than that of the myopathic S1. In addition, control myosin synthetic thick filament length as well as turbidity in solution, measured by light scattering, were twice as large as those of the myopathic heart myosin. These effects induced by myopathy in both filament assembly and turbidity were reversed upon reassociation of IDC myosin with LC2. CONCLUSIONS: The changes in myosin structure and function were linked to a protease-mediated cleavage of LC2 in myosin; a possible role for the protease in the degenerative effects of idiopathic dilated cardiomyopathy is thus defined.

Adenosine Triphosphate↗

PubMed1991

Influence of the cardiac myosin hinge region on contractile activity.

The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, was specific to human, dog, and rat cardiac myosins, did not crossreact with gizzard or skeletal myosin, and had no effect on ATPase activity of purified S1 and myofibrils. However, it completely suppressed the movement of actin filaments in in vitro motility assays and reduced active shortening of sarcomeres of skinned cardiac myocytes by half. Suppression of motion by the anti-hinge antibody may reflect a mechanical constraint imposed by the antibody upon the mobility of the S2 region of myosin. The results suggest that the steps in the mechanochemical energy transduction can be separately influenced through S2.

Amino Acid Sequence↗

PubMed1990

Distribution in tissue sections of the human groEL stress-protein homologue.

A monoclonal antibody (ML30) raised against the 65 kDa heat-shock protein of mycobacteria showed widespread staining of sections from standard paraffin-embedded human tissues. The staining had a granular pattern and was particularly marked in cells with abundant mitochondria. Increased staining was observed in the synovial lining, histocytes and in the endothelium of reactive and rheumatoid synovium; it was also increased in the reactive lung alveolar lining. It is suggested that the antibody identifies an epitope in mitochondria of a protein homologous with the groEL heat-shock protein of bacteria.

Antibodies, Monoclonal↗

PubMed1989

Expression of the SmB' splicing protein in rodent cells capable of following an alternative RNA splicing pathway.

The expression of the SmB and SmB' spliceosome proteins in a variety of cell types and tissues has been investigated. Although SmB is found in all cells studied, the SmB' protein is found only in a small number of rodent cell types. The presence of this protein is correlated with the ability to utilize an alternative pathway of RNA splicing which is not available in most cell types. This is the first demonstration of tissue specific expression of a protein component of the spliceo-some and suggests a role for SmB' in the regulation of some cases of alternative RNA splicing.

Animals↗

PubMed1989

Comparison of ultrasound and lateral chain urethrocystography in the determination of bladder neck descent.

Several methods exist to determine the position of the bladder neck, an important mechanism of urinary continence. Radiologic screening is widespread but involves irradiation and may be imprecise. We compared perineal ultrasound scanning and radiologic scanning of the bladder neck by use of a chain and catheter and found good correlation between the two techniques. Ultrasound scanning is preferred, as it avoids irradiation, is accurate, is portable, and is readily available in most gynecologic departments.

Catheterization↗

PubMed1989

The value of non-contrast-enhanced CT in blunt abdominal trauma.

The usefulness of non-contrast CT, limited to the upper abdomen, in conjunction with conventional IV contrast-enhanced scanning was studied prospectively in 190 patients who had sustained blunt abdominal trauma. In 78, visceral injuries were confirmed at surgery or at follow-up CT. Of the patients with injuries, 14 (18%) had hyperdense hematomas on the non-contrast studies that became isodense after IV administration of contrast material. These hematomas generally were small and posed an immediate threat to life in only one patient (0.5% of all subjects). In 13% of patients with injury (5% of the total), the additional information did influence treatment planning (surgery in two and intensive conservative treatment in eight). Compared with conventional contrast scanning, the combined non-contrast-contrast technique increased the scanning time only by about 5 1/2 min, but it improved the sensitivity and accuracy of CT in detecting visceral injuries from 74% and 84% to 92% and 91%, respectively (p less than or equal to .003 and p less than or equal to .04). Although contrast-enhanced scanning alone accurately depicts visceral injuries requiring surgical treatment, the incorporation of a non-contrast sequence can detect a subgroup of patients who require intensive conservative management with bed rest and close observation. This additional information can be obtained expeditiously, with minimal additional effort or intervention. The use of non-contrast scanning alone is not recommended.

Abdominal Injuries↗

PubMed1987

Sulfate transport in apical membrane vesicles isolated from tracheal epithelium.

Sulfate uptake in apical membrane vesicles isolated from bovine tracheal epithelium is shown to occur into an osmotically sensitive intravesicular space, via a carrier-mediated system. This conclusion is based on three lines of evidence: 1) saturation kinetics; 2) substrate specificity; and 3) inhibition by the anion transport inhibitors SITS and DIDS. The affinity of the transport system is highest in low ionic strength media (apparent Km = 0.13 mM) and decreases in the presence of gluconate (apparent Km = 0.68 mM). Chloride appears to cis-inhibit sulfate uptake and to trans-stimulate sulfate efflux. Cis-inhibition and trans-stimulation studies with a variety of anions indicate that this exchange system may be shared by HCO3-, S2O3(2-), SeO4(2-), and MoO4(2-) but not by H2PO4- or HAsO4(2-). Studies indicate that protons may play two distinct roles in sulfate transport in this system. 1) Their possible modifier role is suggested by the fact that protons affect SO2-4 transport in an uncompetitive manner. 2) The possibility that the proton gradient may act as an energy source for a secondary active transport is indicated by the fact that the imposition of a proton gradient stimulates a transient movement of sulfate in to the tracheal apical membrane vesicle, against its concentration gradient, causing an "overshoot" phenomenon. Our studies show that the carrier-mediated system can function in the absence of chloride. The overshoot observed in the presence of a proton gradient (OH- gradient) indicates that under those conditions the mechanism of transport may be a SO4(2-)-OH- exchange. The fact that chloride cis-inhibits and trans-stimulates SO4(2-) transport indicates that SO2-4 uptake may also occur via a SO4(2-)-Cl- exchange. Studies carried out so far do not enable us to conclude unequivocally whether the tracheal apical membrane system displays two distinct carrier activities (SO4(2-)-Cl-; SO4(2-)-OH-) or one anion exchanger, which like the erythrocyte anion exchanger, may interact with SO4(2-), Cl-, and H+. The fact that the anion transport inhibitors DIDS and SITS inhibit SO4(2-) transport in the presence or absence of chloride suggests that the latter possibility may be the case.

Animals↗

PubMed1986

There are two gene sequences for human apolipoprotein CI (apo CI) on chromosome 19, one of which is 4 kb from the gene for apo E.

A cDNA probe corresponding to the mRNA sequence for apolipoprotein E (apo E) was used to screen two independently-constructed human genomic libraries. Two recombinants (lambda E-2, and lambda E2-1), isolated using the apo E cDNA probe, also contain part or all of the apo CI gene. Hybridisation studies using both apo E and apo CI cDNA probes show that these two genes are in the same orientation and separated by 4 kb.

Apolipoprotein C-I↗

PubMed1979

Hairdressers as caregivers. I. A descriptive profile of interpersonal help-giving involvements.

The interpersonal help-giving behaviors of 90 hairdressers were explored in depth in an interview study. On the average, hairdressers saw 55 customers a week, and talked 25 minutes with each. About one-third of the talking time concerned clients' moderate to serious personal problems--particularly problems with children, physical health, marriage, depression, and anxiety. Hairdressers reported that offering sympathy and support, being lighthearted, just listening, and presenting alternatives were among their most frequent response strategies. Although they often enjoyed fielding clients' personal problems, at times they felt perplexed by them. Hairdressers perceived listening to customers' interpersonal problems to be an important part of their everyday function and expressed a need for professional inputs in that domain.

Adult↗

PubMed1977