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Biomedical subjects

C E Smith

Publications and source records attributed to C E Smith.

At least 253 records · Page 14Linked to original sources

Terminal glycosylation in rat hepatic Golgi fractions: heterogeneous locations for sialic acid and galactose acceptors and their transferases.

Endogenous acceptors for N-acetylglucosamine (GlcNAc), galactose (Gal) or sialic acid (NeuAc) transfer were labeled to high activities when purified hepatic Golgi fractions were incubated with the corresponding radiolabeled nucleotide sugar in the absence of detergent. The in vitro conditions which were optimal for the endogenous glycosylation of GlcNAc and Gal acceptors (Mn2+, ATP) also promoted fusion within a subset of Golgi membranes. Electron microscope radioautography revealed that the majority of NeuAc acceptors were associated with unfused Golgi membranes, whereas the majority of Gal acceptors were localized to fused membranes. GlcNAc acceptors were approximately equally distributed between fused and unfused membranes. Under conditions in which Golgi membrane fusion was absent (-Mn2+), only NeuAc transfer was active. The majority of endogenous NeuAc acceptors were consequently assigned to the more trans regions of the hepatic Golgi apparatus as concluded from a combination of radioautography (NeuAc transfer) and acid NADPase cytochemistry (reactive medial and trans Golgi saccules). The distribution of NeuAc and Gal transferases was assessed after Percoll gradient centrifugation of disrupted Golgi fractions. The median density of NeuAc transferase was lower than that of Gal transferase. The studies are indicative of distinct Golgi components harboring the majority of acceptors and enzymes for terminal glycosylation.

Acetylglucosamine↗

Ser-Leu-Arg-Arg-atriopeptin III: the major circulating form of atrial peptide.

Vasopressin induces a concentration-dependent increase in atriopeptin immunoreactivity in plasma. Rat plasma, rat atrial extract, and synthetic atriopeptin III (APIII) produced parallel displacement curves of iodine-125-labeled APIII binding to specific antiserum. Fractionation of plasma atriopeptin immunoreactivity by reverse-phase high-performance liquid chromatography showed that the major portion consists of two species of low molecular weight peptides in a ratio of 10 to 1. Both peaks exhibited potent vasorelaxant activity, suggesting the presence of the carboxyl terminal Phe-Arg sequence of atriopeptin in each species. Sequence determination of the purified peptides indicated that the major peptide is Ser-Leu-Arg-Arg-APIII and the minor peptide APIII. It appears that the former is the major species of atrial peptide in the rat circulation and that it is the product of selective cleavage of the high molecular weight precursor.

Animals↗

Human bronchial leucocyte proteinase inhibitor. Rapid isolation and kinetic analysis with human leucocyte proteinases.

Bronchial leucocyte proteinase inhibitor (BLPI) is an 11 000 Mr protein found in human mucous secretions. This inhibitor apparently controls the serine proteinases elastase and cathepsin G, released from extravascular polymorphonuclear leucocytes. A simple, single-step chromatographic procedure for the isolation of BLPI based on its affinity for chymotrypsin was developed. The purified inhibitor was homogeneous by electrophoresis and gel filtration. Amino acid analyses were in close agreement with previous reports, and showed BLPI to be rich in proline and cystine, but lacking histidine. We have further characterized the role of BLPI with respect to human leucocyte elastase and cathepsin G by close examination of the kinetic parameters. Additionally, we have determined the kinetics of association (kon) and dissociation (koff) for BLPI with bovine trypsin and chymotrypsin. Equilibrium dissociation constants (Ki) of 1.87 X 10(-10) M, 4.18 X 10(-9) M, 8.28 X 10(-9) M and 2.63 X 10(-8) M were obtained for human leucocyte elastase, cathepsin G, bovine trypsin and chymotrypsin, respectively. These results are discussed with respect to BLPI's possible function in vivo and its role relative to other inhibitors in bronchial secretions.

Amino Acids↗

Granulocytic sarcoma treated as an acute leukemia. Report of a case.

A young man presented with intestinal obstruction. Laparotomy revealed a large mass encircling the cecum and terminal ileum which histologically proved to be a granulocytic sarcoma. No evidence of leukemia was present in peripheral blood or bone marrow. Initial therapy consisted of abdominal irradiation. Two months following completion of irradiation, widespread systemic involvement without leukemia was evident. Systemic chemotherapy with doxorubicin, cytosine arabinoside, vincristine, and prednisone was initiated. Chemotherapy was continued for 18 months. The patient has remained without evidence of disease for 49 months following discontinuation of treatment, and 67 months after initial diagnosis. Systemic therapy for granulocytic sarcoma presenting without evidence of leukemia is reviewed.

Acute Disease↗

Relation between discharge regularity and responses to externally applied galvanic currents in vestibular nerve afferents of the squirrel monkey.

Most vestibular nerve afferents can be classified as regularly or irregularly discharging. Two factors are theoretically identified as being potentially responsible for differences in discharge regularity. The first, ascribable to synaptic noise, is the variance (sigma v2) characterizing the transmembrane voltage fluctuations of the axon's spike trigger site, i.e., the place where impulses normally arise. The second factor is the slope (dmuv/dt) of the trigger site's postspike recovery function. Were (dmuv/dt) a major determinant of discharge regularity, the theory predicts that the more irregular the discharge of a unit, the greater should be its sensitivity to externally applied galvanic currents and the faster should be the postspike recovery of its electrical excitability. The predictions would not hold if differences in the discharge regularity between units largely reflected variations in sigma v. To test these predictions, the responses of vestibular nerve afferents to externally applied galvanic currents were studied in the barbiturate-anesthetized squirrel monkey. Current steps of 5-s duration and short (50 microsecond) shocks were delivered by way of the perilymphatic space of the vestibule. Results were similar regardless of which end organ an afferent innervated. The regularity of discharge of each unit was expressed by a normalized coefficient of variation (CV*). The galvanic sensitivity (beta p) of a unit, measured from its response to current steps, was linearly related to discharge regularity (CV*), there being approximately 20-fold variations in both variables across the afferent population. Various geometric factors--including fiber diameter, position of individual axons within the various nerve branches, and the configuration of unmyelinated processes within the sensory epithelium--are unlikely to have made a major contribution to the positive relation between beta P and CV*. The postspike recovery of electrical excitability was measured as response thresholds to shocks, synchronized to follow naturally occurring impulses at several different delays. Recovery in irregular units was more rapid than in regular units. Evidence is presented that externally applied currents acted at the spike trigger site rather than elsewhere in the sensory transduction process. We argue that the irregular discharge of some vestibular afferents offers no functional advantage in the encoding and transmission of sensory information. Rather, the irregularity of discharge is better viewed as a consequence of the enhanced sensitivity of these units to depolarizing influences, including afferent and efferent synaptic inputs.

Animals↗

Ultrastructural localization of nicotinamide adenine dinucleotide phosphatase (NADPase) activity within columnar, goblet, and Paneth cells of rat small intestine.

The distribution of nicotinamide adenine dinucleotide phosphatase (NADPase) activity was examined in epithelial cells of rat small intestine. Segments of ileum were fixed with glutaraldehyde and tissue chopper sections were incubated for up to 4 hr at pH 5.0 in cytochemical media prepared with NADP as substrate. NADPase activity was found primarily within the Golgi saccules of columnar, goblet, and Paneth cells. Columnar and goblet cells showed most of the NADPase activity within the saccules which were intermediate between the cis and trans faces of the Golgi stack. Paneth cells, however, showed the heaviest staining within saccules between the intermediate and innermost saccule at the trans aspect of the Golgi stack. Both columnar cells and Paneth cells also contained spotty, and sometimes heavy, deposits of reaction product within an occasional focal area of the GERL system and within an occasional lysosome. Control experiments indicated that the Golgi-associated NADPase activity was enhanced if cells were pretreated for about 12 hr with EGTA prior to incubation. No similar enhancement was apparent if the tissues were pretreated with DMSO. Furthermore, NADPase activity within the Golgi saccules could be inhibited completely by incubating intestinal epithelial cells with NADP in the presence of sodium fluoride or L(+)-tartrate.

Animals↗

Process curriculum in nursing contrasted to product orientation.

In summary the major variations in these two conceptions of curriculum include definitions of curriculum and learning, sources of curriculum and instructional content, technical language and underlying these their basic orientations. Yet, the two share intents in the areas of curricular theory, structure, teaching, development, and evaluation. The significance of these differences lies very much on the shoulders of the users of these two conceptions. The selection of one over the other must be gauged against each user's educational priorities and orientation. Implementation of each depends on a full understanding of each model. Even if a strict adherence to one or the other is not pursued, the review of both helps immensely in clarifying the specific concepts and estimating the impact of each model. It is through comparison that the assets and liabilities of each will be identified.

Curriculum↗

Treatment of metastatic colorectal carcinoma with 5-FU, mitomycin, vincristine, and methotrexate.

Fifty-three patients with advanced metastatic colorectal carcinoma were treated every 4-5 weeks with a chemotherapeutic regimen consisting of 5-FU (300 mg/m2 iv on Days 1-5), mitomycin (10 mg/m2 iv on Day 1 only [repeated every other course]), vincristine (0.75 mg/m2 on Days 1 and 5), and methotrexate (8.0 mg/m2 iv on Days 1 and 5). The overall response rate was 43.4%, with three patients (5.7%) achieving complete response (mean duration, 13.3 months) and 20 patients (37.7%) achieving partial response (mean duration, 6.3 months). Stable disease was not considered to be a response category in this report. The mean overall response duration was 7.8 months. The observed mean survival duration in responders was 15.2 months and in nonresponders was 8.9 months (P less than or equal to 0.01). Hematologic and subjective toxic effects are discussed.

Adult↗

Hyperplastic lesions of the primitive meninx of fathead minnows, Pimephales promelas, induced by ammonia: species potential for carcinogen testing.

In our laboratory, fathead minnows were reared from time of hatching to adulthood at 5 concentrations of ammonia in a toxicity test lasting 304 days. The ammonia concentration test range was 9.36 to 30.0 mg NH3-N/liter (0.639 to 2.17 mg NH3/liter). Intracerebral lesions were observed in fish from each ammonia concentration but not in the controls. The severity of the lesions was positively correlated with increased ammonia concentration. Massive hyperplastic lesions developed in fish tested at the 2 highest concentrations. Histologically, lesions appeared to originate from the primitive meninx, which grew into the cranial cavity, and in some fish through the cranium. Based on the orderly appearance of tissues and evidence of regression of lesions, the lesions are not considered to be neoplasms but hyperplasias of primitive meninx tissue induced as a response to ammonia exposure. Fathead minnows (Pimephales promelas) have proved useful for acute toxicity testing of environmental contaminants and have a potential usefulness in carcinogenicity testing. They are easily maintained in the laboratory, can be readily induced to spawn during their first year of life, and have a relatively short period of embryogenesis.

Ammonia↗