Search PubMed⌕ Search

Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 217 records · Page 12Linked to original sources

The effects of malnutrition on secretory and cellular immune processes.

About 15 million children under 5 years of age die each year due to suppressed immunity and the resulting increased infection. In severely malnourished children and animals some immune systems such as T-cell function, secretory IgA and complement are significantly suppressed. Other systems, such as the serum IgG or IgA, are normal or even elevated. Some of these changes are apparently caused by nutritional stress while others may be due to stimulation by increased incidence of infection and antigen load. On the other hand, marginal malnutrition stimulates increased phagocytosis and T-cell function with increased immunity to cancer but decreased resistance to certain microbial agents. The mechanisms of immune suppression by malnutrition, persistence of these effects after renutrition, and the effect of maternal malnutrition on newborn immunity are critically reviewed. Possible non-nutritional means of rapid immunological restoration of malnourished children are described.

Adolescent↗

Mass spectrometry of some permethylated apiosyl nucleosides.

The mass spectra of the permethyl derivatives of a group of synthetic D-apio-L-furanosyl nucleosides were collected and compared with those of their ribosyl analogs. While most of the m/e values are the same between analogous spectra, some of the relative intensities differ markedly. Each spectrum contains characteristics ions which are probably due to fragmentation of the dissimilar sugar moieties.

Mass Spectrometry↗

Synthesis of branched-chain apiosylpyrimidines and their inhibition of lymphocyte proliferation.

Branched-chain nucleosides containing beta-D-apio-L-furanose were synthesized by condensation of the bis(trimethylsiyl) derivative of uracil (11), thymine (12), 5-fromouracil (13), and 5-iodouracil (14) with the protected 1-O-acetylapiose in the presence of a Friedel-Crafts catalyst. D-Apio-L-furanosyluracil (11) and D-apio-L-furanosylthymine (12) show immunosuppressive activity for rat T-lymphocytes stimulated to grow by phytohemagglutinin but exhibit no inhibitory activity against herpes simplex virus. Compounds 11--14 did not inhibit herpes simplex virus replication, while low inhibition was obtained with the one nucleoside containing D-apio-D-furanose, D-apio-D-furanosyladenine. D-Apio-L-furanosyl-5-bromouracil (13), D-apio-L-furanosyl-5-iodouracil (14), bromouridine, and iodouridine suppressed growth of human lymphoblasts significantly more than the nonhalogenated apiosylphrimidines.

Animals↗

Isolation of aminopeptidases from Histoplasma capsulatum.

Two aminopeptidases (arylamidases) were isolated and partially purified from Histoplasma capsulatum. The larger molecular weight enzyme was a proline iminopeptidase and hydrolyzed primarily a synthetic substrate, L-prolyl-beta-napthylamide. The other aminopeptidase was less substrate specific and hydrolyzed rapidly the following amino acid beta-napthylamides (beta NA): L-arginyl-beta NA greater than L-lysyl-beta NA greater than -L-4-methoxy-leucyl-beta NA greater than L-leucyl-beta NA greater than L-phenylalanyl-beta NA greater than L-alanyl-beta NA. The proline iminopeptidase was purified 1420 fold while the leucine aminopeptidase was purified 650 fold with good recovery.

Aminopeptidases↗

The effect of in utero protein malnutrition and subsequent renutrition on rat saliva and some salivary enzymes.

1. Rat pups developed chronic protein insufficiency resulting from malnutrition diet in utero while their dams received 40 g protein/kg diet. 2. Before weaning they were found to have decreased salivary amylase (EC 3.2.1.1) and aminopeptidase activities. 3. A complete diet (250 g protein/kg) rapidly restored salivary amylase activity before weight normalization. However, renourished pups (malnourished pups given 250 g protein/kg for 14 d) still had increased numbers of Streptococcus multans in their plaque.

Aminopeptidases↗

Effect of moderate malnutrition on concentrations of immunoglobulins and enzymes in tears and saliva of young Colombian children.

The influence of moderate malnutrition on immunoglobulins and enzymes in the sera and secretions of 71 Colombian children was studied. Concentrations of immunoglobulin A, immunoglobulin G, lysozyme, albumin, and aminopeptidase were measured in the sera, tears, and saliva of 27 normal, 32 grade I, 9 grade II, and 3 grade III malnourished children. The most severely malnourished children, grades II and III, had markedly reduced immunoglobulin A concentrations and elevated immunoglobulin G concentrations in tears. Immunoglobulin A levels in whole saliva were also reduced in these malnourished children. In contrast, the concentration of immunoglobulin A in the sera of these children was significantly elevated. There was no influence of malnutrition on levels of lysozyme, albumin, total protein, and aminopeptidase in tears or saliva. These results indicate that secretory immunity may be impaired in moderately malnourished children due to decreased levels of immunoglobulin A in secretions.

Aminopeptidases↗

Pancreatic and salivary amylase activity in undernourished Colombian children.

Amylase activities were quantitated in secretions of marginally and severely malnourished Colombian children. In young children with a mean age of 21 months, the relative pancreatic and salivary amylase isozyme activities of urine were significantly changed in marginally malnourished children compared to normal children. There was a relative increase in salivary and decrease in pancreatic amylase activity in the undernourished children and total amylase activity was somewhat decreased. Amylase activity in saliva and tears was significantly lower in these malnourished children. Older children who were more severely malnourished had significantly lower amylase activity in their sera and tears. Thus marginal and severe malnutrition affects the production of amylase by the pancreas and salivary glands of young children distinctly. It significantly suppresses amylase activity in tears, saliva, and serum.

Aminopeptidases↗

Superoxide dismutase activity in polymorphonuclear leukocytes and alveolar macrophages of protein malnourished rats and guinea pigs.

Chronic protein insufficiency in utero was achieved by feeding to rat dams an 8% protein diet beginning before breeding and continuing until weaning. Thereafter, the in utero malnourished pups were fed the 8% protein diet. Superoxide dismutase (SOD), an enzyme which protects against superoxide radical, was quantitated in pellet and supernatant of polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM). The AM of rats malnourished in utero contained 1.7 times as much protein and 3 times as much total SOD activity as the AM of control rats. In PMN of these rats, the amount of protein and SOD activity was the same. Significantly larger number of Streptococcus mutans were located from the dental plaque of the in utero malnourished rats. AM isolated from female guinea pigs fed a 9% protein diet from weaning at 11 days of age contained 1.5 times as much protein and twice as much SOD activity as AM from normal guinea pigs. However their PMN contained smaller amounts of total protein and SOD activity. The malnourished guinea pigs had a mammary gland infection and a prolonged conjunctival infection following inoculation with Guinea Pig Inclusion Conjunctivitis indicating that these animals were more susceptible to these infections. The increase in total SOD activity and in the total amount of protein in AM suggests that chronic protein insufficiency leads to susceptibility to infection and to macrophage activation but has no similar effects on PMN.

Animals↗

Cell-mediated hypersensitivity in guinea-pigs infected with toxoplasms gondii.

This investigation demonstrated delayed hypersensitivity by macrophage migration inhibition (MMI) and skin-testing (ST) at 4, 8, 12, and 17 weeks and by lymphocyte transformation (LT) at 4, 12, and 17 weeks after infection of guinea-pigs (GP) with Toxoplasma gondii (C-37 strain). MMI and LT were both most pronounced at 4 and 17 weeks post-infection. GP immunized with toxoplasmin in complete Freund's adjuvant (CFA) demonstrated positive blast transformation and ST, but GP immunized with phosphate buffered saline in CFA did not. MMI was demonstrated with both immunizing preparations. Positive dye test and indirect hemagglutination test titers from 4 through 17 weeks were found.

Animals↗

Identification of yeast phase of pathogenic fungi by the specificity of their aminopeptidase(s).

Specificity of aminopeptidase(s) was fluorimetrically determined in the yeast phase of Histoplasma capsulatum, H. duboisii, H. farciminosum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Candida albicans and Crytococcus neoformans. After individually incubating each of 26 amino acid-beta-naphthylamides with each yeast, the amount of each amino acid-beta-naphthylamide hydrolyzed was determined by measuring the free naphythylamine. This resulted in a reproducible profile of the aminopeptidase(s) for each fungus when medium, growth time, size of inoculum and incubation period were standardized. This technique provided a rapid and specific means of identification and differentiation among these yeasts. Specific amino acids were identified from the profile of each yeast as those rapidly liberated by the aminopeptidase(s) of that yeast. These amino acids delineated the amino acid requirement for the normal growth of each yeast.

Aminopeptidases↗

Synthesis, characterization and properties of uridine 5'-( -D-apio-D-furanosyl pyrophosphate).

1. A method was developed for synthesizing UDP-apiose [uridine 5'-(alpha-d-apio-d-furanosyl pyrophosphate)] from UDP-glucuronic acid [uridine 5'-(alpha-d-glucopyranosyluronic acid pyrophosphate)] in 62% yield with the enzyme UDP-glucuronic acid cyclase. 2. UDP-apiose had the same mobility as uridine 5'-(alpha-d-xylopyranosyl pyrophosphate) when chromatographed on paper and when subjected to paper electrophoresis at pH5.8. When [(3)H]UDP-[U-(14)C]glucuronic acid was used as the substrate for UDP-glucuronic acid cyclase, the (3)H/(14)C ratio in the reaction product was that expected if d-apiose remained attached to the uridine. In separate experiments doubly labelled reaction product was: (a) hydrolysed at pH2 and 100 degrees C for 15min; (b) degraded at pH8.0 and 100 degrees C for 3min; (c) used as a substrate in the enzymic synthesis of [(14)C]apiin. In each type of experiment the reaction products were isolated and identified and were found to be those expected if [(3)H]UDP-[U-(14)C]apiose was the starting compound. 3. Chemical characterization established that the product containing d-[U-(14)C]apiose and phosphate formed on alkaline degradation of UDP-[U-(14)C]apiose was alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate. 4. Chemical characterization also established that the product containing d-[U-(14)C]apiose and phosphate formed on acid hydrolysis of alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate was d-[U-(14)C]apiose 2-phosphate. 5. The half-life periods for the degradation of UDP-[U-(14)C]apiose to alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate and UMP at pH8.0 and 80 degrees C, at pH8.0 and 25 degrees C and at pH8.0 and 4 degrees C were 31.6s, 97.2min and 16.5h respectively. The half-life period for the hydrolysis of UDP-[U-(14)C]-apiose to d-[U-(14)C]apiose and UDP at pH3.0 and 40 degrees C was 4.67min. After 20 days at pH6.2-6.6 and 4 degrees C, 17% of the starting UDP-[U-(14)C]apiose was degraded to alpha-d-[U-(14)C]apio-d-furanosyl 1:2-cyclic phosphate and UMP and 23% was hydrolysed to d-[U-(14)C]apiose and UDP. After 120 days at pH6.4 and -20 degrees C 2% of the starting UDP-[U-(14)C]apiose was degraded and 4% was hydrolysed.

Carbon Isotopes↗

Immunity to chlamydial infections of the eye. II. Studies of passively transferred serum antibody in resistance to infection with guinea pig inclusion conjunctivitis.

Conjunctival infection of guinea pigs by the chlamydial agent of guinea pig inclusion conjunctivitis confers immunity. However, the mechanism of resistance to this intracellular pathogen is not yet defined. In the study reported here, serum immunoglobulin was passively transferred with resultant titers in excess of those known to be associated with immunity. Nonetheless, when the passive transfer recipients were challenged, they acquired infection which was neither delayed nor attenuated. Eye secretion antibody titers appeared and increased only after 11 days of infection in both passive transfer recipients and control groups, suggesting but not proving de novo local synthesis of secretory antibody. This study suggests that cellular or secretory immune mechanisms may predominate in resistance to this infection.

Animals↗