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Biomedical subjects

R M Mulligan

Publications and source records attributed to R M Mulligan.

At least 37 records · Page 2Linked to original sources
PubMed1985

Inhibition and stimulation of ribulose-1,5-bisphosphate carboxylase/oxygenase by glyoxylate.

Glyoxylate is a slowly reversible inhibitor of the CO2/Mg2+-activated form of ribulose-1,5-bisphosphate carboxylase/oxygenase from spinach leaves. Inactivation occurred with an apparent dissociation constant of 3.3 mM and a maximum pseudo-first-order rate constant of 7 X 10(-3) s-1. The rate constant for reactivation was 1.2 X 10(-2) s-1. Glyoxylate did not cause differential inhibition of ribulosebisphosphate carboxylase or oxygenase activities. 6-Phosphogluconate protected the enzyme from inactivation by glyoxylate. Glyoxylate was incorporated irreversibly into the large subunit of ribulosebisphosphate carboxylase after reduction with sodium borohydride. Activated enzyme incorporated 1.3 mol of glyoxylate per mole protomer, while enzyme treated with carboxyarabinitol 1,5-bisphosphate (CABP) to protect the active sites incorporated only 0.3 mol glyoxylate per mole protomer. The data suggest that glyoxylate forms a Schiff base with a lysyl residue in the region of the catalytic site. Glyoxylate stimulated the activity of the unactivated enzyme by about twofold. Pseudo-first-order inactivation also occurred with the unactivated enzyme after the initial stimulation by glyoxylate, although at a much slower rate than with the activated enzyme. Glyoxylate treatment of partially activated enzyme did not stimulate formation of the quaternary complex of enzyme X CO2 X Mg2+ X CABP.

Enzyme Activation↗
PubMed1983

The lability of an intermediate of the ribulose bisphosphate carboxylase reaction.

Interruption of the catalytic cycle of ribulose-bisphosphate carboxylase by acid denaturation liberated an intermediate with a labile phosphate ester. Addition of fresh, buffered carboxylase enzyme to the acidified carboxylase reaction after 5 s inhibited phosphate release from the intermediate. Therefore, the species with a labile phosphate ester was stable for 5 s in acid and was apparently a substrate for the enzymatic reaction, since the labile intermediate was converted to a stable form by the protein. After acid denaturation, the carboxylated intermediate could be stabilized by reduction after 5 s in acid, but after 1 h no carboxylated intermediate remained. The stoichiometries of phosphate released to enzyme active sites and the carboxylated intermediate trapped to enzyme active sites were approximately 0.04. It was concluded that the labile phosphate species is probably the carboxylated intermediate rather than the enediol(ate) intermediate. The carboxylase and oxygenase reactions were probed for intermediates by the ability of the enzymatic reaction to reduce hexacyanoferrate(III), dichlorophenolindophenol, or nitroblue tetrazolium. Reduction of these reagents and hexacyanoferrate(III)-dependent paracatalytic inactivation were not observed. The copper chelate of lysine, a superoxide dismutase active species, did not selectively inhibit ribulose-bisphosphate oxygenase.

Binding Sites↗
PubMed1983

Effects of glyoxylate on photosynthesis by intact chloroplasts.

Because glyoxylate inhibits CO(2) fixation by intact chloroplasts and purified ribulose bisphosphate carboxylase/oxygenase, glyoxylate might be expected to exert some regulatory effect on photosynthesis. However, ribulose bisphosphate carboxylase activity and activation in intact chloroplasts from Spinacia oleracea L. leaves were not substantially inhibited by 10 millimolar glyoxylate. In the light, the ribulose bisphosphate pool decreased to half when 10 millimolar glyoxylate was present, whereas this pool doubled in the control. When 10 millimolar glyoxylate or formate was present during photosynthesis, the fructose bisphosphate pool in the chloroplasts doubled. Thus, glyoxylate appeared to inhibit the regeneration of ribulose bisphosphate, but not its utilization.The fixation of CO(2) by intact chloroplasts was inhibited by salts of several weak acids, and the inhibition was more severe at pH 6.0 than at pH 8.0. At pH 6.0, glyoxylate inhibited CO(2) fixation by 50% at 50 micromolar, and glycolate caused 50% inhibition at 150 micromolar. This inhibition of CO(2) fixation seems to be a general effect of salts of weak acids.Radioactive glyoxylate was reduced to glycolate by chloroplasts more rapidly in the light than in the dark. Glyoxylate reductase (NADP(+)) from intact chloroplast preparations had an apparent K(m) (glyoxylate) of 140 micromolar and a V(max) of 3 micromoles per minute per milligram chlorophyll.

Journal Article↗
PubMed1981

Parenteral nutrition program in a major cancer center.

In this article, formulation ordering, manufacturing procedures, and the quality control techniques utilized by the parenteral nutrition program at Memorial Sloan-Kettering Cancer Center are described. The cancer patient's metabolic status frequently changes; therefore, individualized prescriptions are used for all parenteral nutrition solutions. Due to the cancer patient's high risk of infection, related to disease-induced or iatrogenic immunosuppression, strict attention to aseptic procedures is required, including personnel wearing disposable gowns, head and shoe coverings, face masks, and surgical gloves. Specific emphasis has been placed on maximal cost effectiveness in manufacturing protocols. Preparation of solutions is, however, only one component of the role played by the pharmacists on the nutrition team. We describe the clinical responsibilities which are of paramount importance, since medications and other treatment modalities can markedly alter nutritional status and electrolyte balance. Monitoring the medications a patient receives and carefully watching a patient's laboratory results are important functions of the pharmacist. For the cancer patient, particular emphasis must be placed on nutritional and metabolic aberrations caused by antibiotics, corticosteroids, diuretics, antineoplastic agents, and narcotic analgesics. Radiation therapy can result in serious physiologic and nutritional effects. An innovative patient profile for monitoring a cancer patient receiving parenteral nutrition is introduced. The pharmacists are also involved in several teaching programs and a new outpatient program for administration of I.V. antibiotics to selected home total parenteral nutrition patients.

Cancer Care Facilities↗
PubMed1980

Properties of a Membrane-bound Phosphatase from the Thylakoids of Spinach Chloroplasts.

A 3-phosphoglycerate phosphatase activity of about 2 micromoles per minute per milligram chlorophyll is associated with the thylakoid membranes of spinach chloroplasts. The K(m) for 3-phosphoglycerate is 3 millimolar. The enzyme can be solubilized from thylakoid membranes by treatment with 0.33 molar MgCl(2) or sodium deoxycholate. The activity is not stimulated by sulfhydryl reagents or the addition of 10 millimolar MgCl(2). The enzymic activity is insensitive to ethylenediaminetetraacetate. The pH optimum is broad, between 5.5 to 7.5. Although the substrate specificity is broad, 3-phosphoglycerate is the best substrate of those tested at neutral pH. However, p-nitrophenyl phosphate was a more effective substrate at pH 5.5. The enzyme exhibits the general characteristics of an acid phosphatase.

Journal Article↗
PubMed1976

A survey of epithelial inclusions in the ovarian cortex of 470 patients.

The ovaries of 470 patients obtained for various indications at operation revealed 178 with 193 ovarian cysts and tumors - including 63 serous, 23 endometrial, and 27 mucinous - as well as 103 with tubal (serous), 35 with endometrial, and 2 with cervical (mucinous) epithelial inclusions. A very high frequency of transformation of mucinous epithelial inclusions into cysts and tumors contrasted with about 40% similar transformation of serous and endometrial inclusions into cysts and tumors.

Adolescent↗
PubMed1975

Pathogenesis of teratoid tumors of the ovary and testis.

Based upon a representative sample of testicular tumors studied at the Armed Forces Institute of Pathology, several testicular and ovarian tumors observed in Denver, pertinent papers in the literature, and the singular thesis of Chevassu on tumors of the testis, the pathogenesis of such neoplasms is elaborated. The findings are philosophical, speculative, and established. Man is a multicellular individual to be regarded as a vehicle for the transmission of unicellular organisms or germ cells from one generation to the next. These cells remain distinct from somatic and trophoblastic cells. The mature human female not only tolerates the normal expression of the fertilized ovum during pregnancy (sex cells, blastoderm, and trophoblast) but also seems capable of greater differentiation of immature somatic cells resulting from parthenogenesis of one or more ova into cells of the three germ layers, as well as the suppression of the growth of neoplastic sex cells and trophoblast cells, with benign cystic teratoma as the most common culmination. The preponderance of malignant teratoid tumors before sexual maturity is a corollary. In contrast, the human male is not equipped with organizers postulated for the human female and thus is unable to differentiate malignant immature somatic cells, the most common cancerous element in testicular tumors. The explanation for such neoplasms must be on the basis of segregation of such cells and abnormal spermatogonia or less often trophoblastic cells in the embryo, with later expression as neoplastic cells, since spermatogonia and progeny are unable to form a new individual. To paraphrase Wilms, the statement may be made that malignant testicular and ovarian tumors of teratoid type are related, despite their different microscopic appearance, to a common form. They differ only in the quality, not in the quantity, of the different tissues comprising them. These tumors contain neoplastic blastodermic cells and differentiated cells of the three germ layers, neoplastic sex cells, and neoplastic trophoblastic cells. The cells of these tumors and the tissues they form resemble very nearly the tissues of the human embryo with nonaxial formation of alimentary and respiratory structures in many instances. The notable frequency of variably differentiated neural elements in the teratoids tumors of the ovary is in sharp contrast to their uncommon occurrence in like tumors of the testis. Dysgenesis of the ovaries and the testes of testicular feminization syndrome should be regarded as likely soil for the development of teratoid tumors.

Adolescent↗
PubMed1975

Mammary cancer in the dog: a study of 120 cases.

Of the 120 cases of mammary cancer occurring in 117 female dogs (15 spayed), 2 male dogs, and 1 dog of undetermined sex, 107 (nearly 90%) were observed in dogs 8 to 15 years old. Mammary tumors occurred in nearly 14% of 875 female dogs with neoplasms. Nearly 60% of 128 neoplasms were located in the 4th and 5th mammary glands. Of the 128 cancers in these 120 dogs, 85 were classified as duct carcinoma, 38 as lobular carcinoma, 3 as malignant mixed tumor, and 2 as duct and lobular carcinomas. Most duct carcinomas originated in the epithelial cells of ducts at all levels, and a few arose in previously benign duct papillomas. The lobular carcinomas arose in alveoli and developed into progressively larger lobules. A negative factor in the development of mammary cancer is ovariectomy before or shortly after the first estrous cycle in the dog and before the age of 40 in women. In both dog and man, aging is a positive factor in the development of mammary cancer. In women, other positive factors are nulliparity and inheritance; e.g., a high rate of breast cancer in close female relatives of Jewish extraction. An epidemiologic study of breast cancer in man and dog in high-risk countries(e.g., United States) and low-risk countries (e.g., Japan) is indicated.

Animals↗
PubMedDate not supplied

Distribution of maize mitochondrial transcripts in polysomal RNA: evidence for non-selectivity in recruitment of mRNAs.

The distribution of maize mitochondrial transcripts in polysomal RNA fractions obtained from root tissue, shoot tissue, or isolated intact mitochondria was analyzed. The distribution of cox3 transcripts that differ in 5' untranslated RNA sequence was similar in total polysomal and total mitochondrial RNA fractions, suggesting that 5' heterogeneity does not affect recruitment of transcripts into the polysomal RNA. The distribution of spliced and unspliced cox2 transcripts was also analyzed in polysomes from total tissue or isolated mitochondria, and both precursor and mature mRNAs were present in the high-molecular-weight RNA fraction. These results suggest that ribosomal association with mitochondrial transcripts is not selective.

Base Sequence↗