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Biomedical subjects

R E Kelly

Publications and source records attributed to R E Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1987

Prevention of suction-induced hypoxemia by simultaneous oxygen insufflation.

The effects of endotracheal suctioning were studied in 38 patients. A significant decline in arterial oxygen tension and saturation was noted in all patients. A new double lumen suction catheter that simultaneously insufflates oxygen while suctioning was tested in these same patients and was found to prevent hypoxemia in all patients. We recommend that the insufflation catheter be added to the protocol of hyperventilation with 100% oxygen to help prevent suction-induced hypoxemia.

Cardiac Surgical Procedures↗
PubMed1986

The dihydroorotase domain of the multifunctional protein CAD. Subunit structure, zinc content, and kinetics.

Dihydroorotase (DHOase) catalyzes the third step in eukaryotic de novo pyrimidine biosynthesis. In mammalian cells, this enzyme activity is carried by a large chimeric protein, CAD, that also catalyzes the first two steps in the pathway: glutamine-dependent carbamyl phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). Controlled elastase cleavage of CAD released a 44,000 +/- 2,000-dalton proteolytic fragment which catalyzed only the dihydroorotase reaction. We have devised a rapid and simple method for the isolation of the DHO domain from elastase digests. The domain, which was obtained in 36% yield, was found to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing. The domain was also characterized by amino acid analysis and analytical high pressure liquid chromatography peptide mapping. The amino terminus of both the DHO domain and intact CAD was blocked suggesting that this domain is located at the extreme amino terminus of the CAD polypeptide, a result consistent with the suspected juxtaposition of domains as DHO-CPS-ATC. The isoelectric point of the DHO domain was 5.1, while that of the ATC domain was 9.4, so that the ends of the CAD polypeptide are oppositely charged at physiological pH. Immunoblotting with DHO domain-specific antibodies showed that a 47-kDa species was generated in the early stages of controlled proteolysis of CAD. Thus there are two elastase cleavage sites within a 3-kDa connecting region that links the DHO and CPS domains. The domain was shown by atomic absorption spectrophotometry and by isolating a 65Zn-containing DHO domain from mammalian cells grown in the presence of the radionuclide to contain 1 g eq of tightly bound zinc in each polypeptide chain. Zinc was not found in any other CAD domain. Chelating agents inhibit dihydroorotase activity of the isolated domain supporting the conclusion, based on studies of intact CAD by others, that zinc participates in catalysis. At moderate protein concentrations the DHO domain was a 88,000 dimer with a Stokes radius of 37.6 A, a S20,w = 5.1 X 10(-13) s, a diffusion coefficient of 3.17 X 10(-7) cm2 s-1, and a frictional ratio of 1.26. On dilution the dimer dissociated and was in rapid concentration-dependent equilibrium with a 43,500 monomer. The hydrodynamic parameters of the monomer have also been estimated (Stokes radius of 29.8 A, D20,w = 4.11 X 10(-7) cm2 s-1, and f/f0 1.21).(ABSTRACT TRUNCATED AT 400 WORDS)

Amidohydrolases↗
PubMed1985

Sodium butyrate induced alterations in lysosomal enzyme activity.

Treatment of cultured HeLa cells with 5 mM sodium butyrate causes an inhibition of growth as well as extensive chemical and morphological differentiation. Lysosomal enzyme activity changes have been associated with both normal and neoplastic growth as well as many aspects of the neoplastic process. The comparative ultrastructural results show that the butyrate-treated cells have a more extensive internal membranous system than the untreated cells, whereas other organelles seem unaffected by the butyrate treatment. Methods for the histochemical localization of lysosomal acid phosphatase show a twofold increase in particulate reaction product in the butyrate-treated HeLa cells. Isolation of lysosomes followed by a comparative enzyme analysis shows a two to three fold increase in acid phosphatase activity per cell after 24 h of butyrate treatment, as well as three to four fold increase in beta-glucuronidase activity. These increases reverse within 24 h of removal of the butyrate from the culture medium. These results as interpreted suggest that butyrate treatment may be preventing sublethal autolysis by arresting the leakage of the lysosomal enzymes from the lysosome into the cytosol and thus allowing the cell to chemically and morphologically differentiate.

Acid Phosphatase↗
PubMed1985

Oligomeric structure of the multifunctional protein CAD that initiates pyrimidine biosynthesis in mammalian cells.

The first three steps in mammalian de novo pyrimidine biosynthesis are catalyzed by the multifunctional protein designated CAD. Regions of the single 240-kDa poly-peptide chain are folded into separate structural domains that have discrete functions. Previous studies suggested that CAD forms predominantly trimers. The trimers are found to be in slow equilibrium with hexamers and higher oligomers composed of multiples of three copies of the CAD polypeptide chain. However, quantitative chemical crosslinking studies of CAD with dimethyl suberimidate were used here to show a progressive conversion of monomer to crosslinked hexamer. High levels of the hexamer accumulate in the reaction mixture, suggesting that the major oligomeric form is hexameric, although residual amounts of smaller oligomers remain present. Larger oligomers may form by association of hexamers and are seen after longer crosslinking times. Sucrose gradient centrifugation shows a 20.8S species to be the slowest sedimenting peak, while the larger species sediments at 27.9S. Electron microscopic studies of rotary-shadowed preparations of CAD have confirmed that, while small amounts of other oligomeric forms are present, the CAD monomer is primarily associated into cyclic hexamers with an open planar appearance.

Animals↗
PubMed1985

Structural changes in the contractile apparatus of the myometrium during estrus and pregnancy.

The ultrastructure of the smooth muscle of the uterus of cats was studied at estrus and at several periods during pregnancy. For the pregnancy studies myometrium was observed at 10, 14, 17, 21, and 50 days postcoitus (PC) as well as in five animals close to term (60-63 days PC). Both thick and thin filaments are observed at estrus in five of the six animals studied and also in all of the animals up to 14 days PC. There is a variable occurrence of thick filaments between 14 and 21 days PC at which time thick filaments are not observed over the implantation site but are observed in myometrial tissue taken away from the nidus. Only thin filaments are observed in the myometrium of the pregnant cat after 21 and before 60 days PC. Prior to term there is again a variable occurrence of thick filaments with thick filaments observed in only one of the five animals studied between 60-63 days PC. These results may implicate the fetoplacental complex in the assembly and disassembly of the thick filaments of uterine smooth muscle. The relationship between thick filament assembly, phosphorylation and the parameters regulating uterine contractility are complex and the variable occurrence of thick filaments at the end of term may implicate factors other than hormonal fluctuations, such as stretch and oxytocics, in this process.

Animals↗
PubMed1981

Hormonal effects on the contractile apparatus of the myometrium.

The effect of estradiol-17 beta (E2) and progesterone (P) on the structure of myofilaments of the smooth muscle of the myometrium of cats was studied by electron microscopy. Animals which had been ovariectomized for at least four weeks were divided into three treatment groups. Group I received no additional treatment. Group II animals were treated for 14 days with E2, and Group III animals were treated for 14 days with E2 and then with E2 and P. The smooth muscle of the uterus of Group I animals displayed a single array of thin (less than 10nm) filaments only. Group II animals displayed in all cases a double array of thick (14-16 nm) filaments, whereas Group III exhibited a single array of thin (6-8 nm) filaments only. These results suggest that E2 induces assembly of thick filaments in ovariectomized cats while P promotes thick filament disassembly. It is suggested that this alteration of the structure of the thick filament may be involved in the mechanism by which these hormones alter the contractile activity of the myometrium during estrus, pregnancy, and at parturition.

Animals↗
PubMed1981

Abnormal regulation of in vitro IgG production in multiple sclerosis.

A pokeweed mitogen-stimulated IgG synthesis assay was used to evaluate T suppressor cell function in peripheral blood lymphocytes (PBL) obtained from multiple sclerosis (MS) patients. Autochthonous cultures of fractionated and recombined MS B and T cells exhibited less suppression of IgG synthesis than similar cultures of PBL from control subjects. No difference occurred in the levels of suppression among MS patients grouped according to disease states. When allogenic cultures of MS B and normal T cells or normal B and MS T cells were compared to autochthonous cultures of control cells, no differences were observed. The results suggest that the lower levels of suppression observed in autologous MS cell cultures are not a result of T suppressor cell dysfunction alone.

B-Lymphocytes↗
PubMed1980

Organic convergence spasm.

Convergence spasm has frequently been reported as a hysterical manifestation. A case presenting with this sign and diphenylhydantoin intoxication is described. Other previously reported organic associations are discussed. Convergence spasm may be seen in association with significant organic disease of the nervous system affecting the cerebral hemispheres, the brain-stem, or both.

Adolescent↗
PubMed1979

Hereditary sensory neuropathy with spastic paraplegia.

Five cases of spastic paraplegia with a progressive symmetrical sensory neuropathy producing ulceration and osteomyelitis of the hands and feet are reported. The pathology in one patient, who died of secondary amyloidosis, was similar to that found by Denny-Brown in hereditary sensory radicular neuropathy with severe loss of posterior root ganglion cells and loss of myelinated fibres in both peripheral nerves and posterior columns of the spinal cord. A sural nerve biopsy in another case showed a striking loss of both myelinated and unmyelinated fibres, with some evidence of degeneration and regeneration. The inheritance is probably by an autosomal recessive gene. The prognosis in the more severe form of the disorder is poor.

Adolescent↗
PubMed1976

Horner's syndrome and headache due to carotid artery disease.

Horner's syndrome was accompanied by ipsilateral pain in the head, face, or neck in eight patients. In all cases angiography showed narrowing of the internal carotid artery in a pattern compatible with dissection within the arterial wall. In one patient in whom this diagnosis was substantiated by surgical exploration biopsy of the arterial wall showed changes typical of cystic medial necrosis. It is suggested that this clinical presentation constitutes a distinct syndrome.

Adult↗