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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 649 records · Page 36Linked to original sources

Lens proteins are substrates for the reticulocyte ubiquitin conjugation system.

In the aged lens postsynthetically altered molecules comprise the majority of lens proteins. Many proteolytic activities have been observed in lens supernatants. Since damaged or altered proteins are usually selectively and rapidly degraded in other cells and tissues, the accumulation of these species in the lens seemed enigmatic. Initiation of proteolysis has been studied most extensively in reticulocytes and ts 85 cells. In these systems proteolysis is absolutely ATP dependent, occurs effectively on high molecular weight substrates and, at least for a majority of proteolytic reactions, requires conjugation of ubiquitin to putative substrates. It seemed plausible that the accumulation of high molecular weight protein aggregates in older lenses might be due to the attenuated function of these ubiquitin- and ATP-dependent components in the initial committing processes of proteolysis. This research shows that: ubiquitin is present in the lens; lens proteins are conjugated to 125I-ubiquitin using reticulocyte conjugating systems; the reaction is ATP dependent; proteins from lens epithelium/outer cortex and core form different ubiquitin conjugates; lens proteins compete with lysozyme and reticulocyte proteins for the ubiquitin conjugating apparatus; most of the conjugates are of very high molecular weight; there is a temporal nature to the pattern of conjugates observed; and the ubiquitin conjugation system shows extreme selectivity.

Animals↗

Comparison of iodine-131 OIH and technetium-99m MAG3 renal imaging in volunteers.

Animal studies have suggested that the nonisomeric N3S triamide mercaptide ligand, 99mTc mercaptoacetyltriglycine (MAG3), may provide a satisfactory 99mTc-labeled replacement for 131I hippurate (OIH). Sequential 30-min [99mTc]MAG3 (5-10 mCi) and [131I]OIH (300 microCi) imaging studies were performed in ten normal volunteers in order to compare the image quality, renal excretion, blood clearance, and time to peak height of the renogram curve. In addition, [99mTc] MAG3 (5 mCi) and [131I]OIH (150 microCi) were administered simultaneously in eight volunteers for comparison of 180-min blood and plasma clearances and urine excretion. In the sequential imaging studies, the blood clearance of [99mTc]MAG3 was more rapid than [131I]OIH with a mean clearance of 1.30 l/min compared with 0.88 l/min for [131I]OIH (p less than 0.05). Seventy-three percent of the injected dose of the MAG3 was excreted by 30 min compared with 66.8% for [131I]OIH. Whole kidney and cortical renogram curves showed no significant difference in the time to peak height for MAG3 and [131I]OIH. In all subjects, the quality of the [99mTc]MAG3 images were clearly superior to [131I]OIH. Following simultaneous injection, blood and plasma clearances for [131I]OIH were more rapid than MAG3 when determined for multiple time intervals from 0-30 to 0-180 min (p less than or equal to 0.05). The 0-30-min clearances of MAG3 and [131I]OIH were only slightly greater than the 0-180-min clearances and can be used to obtain valid comparisons of the two agents. As in the sequential study, 30-min urine excretion was greater for MAG3 than [131I]OIH (73.1 compared with 69.6%) but the difference was not statistically significant. Although the differences in the MAG3 clearances following sequential and simultaneous administration are not satisfactorily explained, the fact that both clearances were rapid, the MAG3 and OIH renogram curves were quite similar, and 30-min urine excretions of MAG3 and OIH were essentially identical suggests that MAG3 may become a 99mTc replacement for [13I]OIH and further clinical evaluation is warranted.

Blood Proteins↗

Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function.

A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A [99mTc]dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.

Acute Kidney Injury↗

Advantage of indium-111 leukocytes over ultrasound in imaging an infected renal cyst.

Indium-111-labeled leukocyte scanning is a highly sensitive and specific method of detecting abscesses. This report describes a patient with polycystic kidneys and a single infected cyst. Ultrasound could not determine which cyst was infected, but the infected cyst could be localized by [111In]leukocyte imaging in conjunction with a [99mTc]DMSA renal scan. The two radionuclide studies were used to identify an infected renal cyst and direct ultrasound guided aspiration.

Adult↗

Potential pitfall of DMSA scintigraphy in patients with ureteral duplication.

A 5-wk-old male presented with radiographic findings of a duplicated collecting system. A [99mTc]DMSA scan was requested to evaluate cortical function. Images obtained immediately. postinjection showed activity restricted to the upper poles; in contrast, delayed images at 4 hr showed activity in the bladder and throughout both kidneys. Catheterizing the patient drained the activity from the bladder but had little effect on the refluxed renal activity. The early [99mTc]DMSA images were critical in making the proper interpretation. Technetium-99m DMSA is excreted into the urine and this fact needs to be considered when interpreting scans of patients with possible reflux or obstruction. When DMSA scans are obtained in pediatric patients with possible reflux, catheterization prior to the study and early images prior to the appearance of DMSA in the collecting system are recommended.

Humans↗

Maternity services: the consumer's view.

Findings are reported from a study designed to compare consumer perception of a range of maternity provision. Detailed exploratory work was followed by a pilot study and a postal survey to which 562 mothers responded. An analysis of the data indicated a strong preference for the antenatal and postnatal services provided by general practitioners or neighbourhood hospitals. Although the ratings given to all hospitals for care during labour and delivery were broadly similar, the majority of mothers would prefer a delivery under general practitioner care where considerations of safety permit. Important characteristics of the preferred services are accessibility, continuity, personalized and small-scale care, and recognition of childbirth as a life event. The desirability of retaining a range of services is discussed.

Consumer Behavior↗

The comparative effects of the argon, Nd: YAG, and argon-pumped dye lasers on human platelets and erythrocytes in vitro.

The effects of three lasers, Argon, Nd:YAG, and Argon-pumped Dye, on three types of platelet preparations were evaluated. Either EDTA or buffered citrate served as anticoagulants. Platelets separated from plasma and suspended in buffer showed no decrease in counts following lasering, but morphologic damage was evident with transmission electron microscopy (TEM). In platelet-rich plasma, a fall in counts was noted for the Argon and the YAG (at high energy only) but was absent when the Dye laser was employed. Morphologic damage (TEM), however, was noted with all three lasers. When whole blood preparations were used, more marked changes in both RBCs and platelets were seen in samples collected in EDTA compared with citrated samples. Morphologic damage (TEM) to platelets and RBCs occurred with all three lasers. An artifactual increase in "platelet counts," the appearance of spherocytes, and an increase in plasma Hb indicated RBC injury. Both platelets and erythrocytes were sensitive to variations in power (wattage) despite constant total energy delivery.

Blood Platelets↗

The sfiA11 mutation prevents filamentation in a response to cell wall damage only in a recA+ genetic background.

N-alpha-palmitoyl-L-lysyl-L-lysine dihydrochloride ethyl ester (PLL) at sublethal doses causes filamentous growth of E. coli strains except sfiA mutants, which divide normally in its presence. PLL does not elicit the SOS responses as judged by lambda prophage induction, an increase of RecA protein synthesis or induction of the sfiA operon in a sfiA::lacZ fusion strain. Thus, it appears that filamentation caused by PLL is not an SOS function and might be the result of membrane damage by PLL, which is an amphipathic compound and at higher doses causes cell lysis. This indicates that basal levels of the sfiA gene product are sufficient to inhibit cell division in the presence of PLL. We have found further that the phenotype of the sfiA mutation in the presence of PLL requires a recA+ genetic background and does not occur in E. coli recA1 sfiA11, recA13 sfiA11, recA56 sfiA11 and recA441 sfiA11. All these strains, but rec441 sfiA11, however, regain the ability of sfiA11 mutants to divide in the presence of PLL after transformation with the RecA overproducing-plasmid pXO2. This supports the conclusion that the RecA protein positively affects sfiA11-mediated cell division in the presence of the cell membrane damaging compound, PLL. The basal level of the RecA protein in the recA+ sfiA11 strain is sufficient for this process. An increased level due to overproduction from the multicopy plasmid pXO2 exerts the same effect.

Cell Division↗

Purification, preliminary characterization, and immunological comparison of hog lens leucine aminopeptidase (EC 3.4.11.1) with hog kidney and beef lens aminopeptidases.

Leucine aminopeptidase (LAP) was purified from hog lenses by application of the Himmelhoch procedure for isolation of hog kidney LAP [S. R. Himmelhoch (1970) in Methods in Enzymology (Perlmann, G. E., and Lorand, L., eds.), Vol. 19, pp. 508-513, Academic Press, New York.] This involved treating crude hog lens homogenates with hexadecyltrimethylammonium bromide, DEAE-cellulose adsorption and elution, ammonium sulfate fractionation (53-84% of saturation), and gel filtration on a Bio-Gel A-1.5m column. Purifications ranging from 2080- to 4700-fold with activity yields from 28 to 100% were achieved. The hog lens LAP appeared homogeneous by native and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE). Bio-Gel chromatography of the native enzyme and SDS-PAGE of dimethylsuberimidate-crosslinked LAP indicated a molecular weight of 326,000. SDS-PAGE of untreated LAP showed a subunit weight of 54,000, consistent with a hexameric enzyme structure. By immunodiffusion, LAP from hog lens and kidney were identical while hog lens and beef lens enzymes demonstrated only partial identity. Electrophoresis of the native enzymes showed a slightly lower mobility for the hog lens LAP than for beef LAP at pH 8.7.

Animals↗

Development of an air displacement method for whole body volume measurement of infants.

An infant enclosed in a rigid-walled chamber displaces a volume of air equal to its own volume. The volume of air displaced can be estimated by the change in pressure produced by a standard reduction in the chamber's volume according to Boyle's law. An instrument embodying this principle has been developed in which the differential pressure between two identical chambers is measured during equal sinusoidally imposed volume changes in the two. Problems arising from variable departure of conditions of pressure cycling, from isothermal towards adiabatic, have been dealt with by empirically derived corrections. Data are presented on the use of the method for low birth-weight infants.

Animals↗

The clinical use of radionuclide bone marrow imaging.

Bone marrow aspiration and biopsy are excellent techniques for evaluating bone marrow, but this evaluation is limited to a small part of the total blood-forming organ. With the introduction of radionuclide bone marrow imaging, a simple technique became available that overcomes marrow sampling errors by giving a total body view of functioning marrow. Furthermore, the procedure is noninvasive and provides an atraumatic method for evaluating a number of clinical problems including a discrepancy between bone marrow histology and clinical status (possible marrow sampling error), the determination of amount of active marrow after radiation and chemotherapy when further therapy is being considered, detection of sites of extramedullary hematopoiesis, location of the optimal sites for bone marrow biopsy, the diagnosis and staging of diffuse hematologic disorders, detection of metastases, the diagnosis of bone marrow infarcts in hemolytic anemias, and detecting avascular necrosis of the femoral heads. There are two major classes of bone marrow agents: (1) those that are incorporated into the erythroid precursors such as radioiron and (2) colloids that are taken up by the reticuloendothelial system (RES). Indium-111 chloride was originally considered to be an erythropoietic agent but appears to share some properties of RES labels. The best label to use is dependent on the disease being evaluated.

Anemia, Aplastic↗

Biosynthesis of EGF receptor, transferrin receptor and colligin by cultured human keratinocytes and the effect of retinoic acid.

The biosynthesis of EGF and transferrin receptor by human keratinocytes in culture has been followed using specific monoclonal antibodies. In addition, keratinocytes are shown to synthesise a Mr 47 000 protein that binds to gelatin-Sepharose. Peptide mapping confirms the identity of this protein with colligin, a newly described cell surface-associated glycoprotein that also binds to native collagens (Kurkinen et al., J biol chem 259 (1984) 5915) [9]. Vitamin A and its analogues have profound effects on the differentiation, morphology and motility of human keratinocytes in culture. We show here that retinoic acid (RA) has no effect on the growth rate of the cells or the synthesis of EGF receptor and colligin, but stimulates the synthesis of transferrin receptor.

Antibodies, Monoclonal↗

Therapeutic uses of trace elements.

The properties of trace elements which feature in their therapeutic activity are: binding to macromolecules (enzymes, nucleic acids, etc.) with disturbance of biological function, and interaction with other elements. These properties, particularly the binding to large molecules, are far from specific, an observation which is reflected in the very wide range of diseases in which trace elements are employed. While metal compounds have been administered for several centuries, the scientific basis for treatment with trace elements began with the use of gold compounds, initially in patients with tuberculosis and later those with rheumatoid arthritis. Although many other drugs have been developed, some of which also include metal complexes, gold has retained an important position in the treatment of this condition. The gold-induced effects upon the immunological aspects of RA are also observed in other conditions with autoimmune involvement. The antineoplastic potential of metal complexes will be further exploited by the development of less toxic compounds--of platinum and possibly also of other metals. At the same time there are improvements in the protocols for administration which increase the range of cancers responding to treatment. Perturbation of gastrointestinal activity represents another area where trace elements have an important therapeutic role, both in the control of intraluminal acidity and in the adjustment of nutrient availability. A fourth significant area of trace element therapeutics involves the central nervous system where the use of lithium has provided spectacular results in the treatment of affective and other disorders. With a very wide range of other conditions in which they are employed, therapeutic uses provide somewhat unusual illustrations of the importance of trace elements in human disease.

Arthritis, Rheumatoid↗