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Biomedical subjects

G Dawson

Publications and source records attributed to G Dawson.

306 records · Page 17Linked to original sources
PubMed1969

New technique for enzymic hydrolysis of glycosphingolipids.

A method is described for the study of glycosyl ceramide glycosyl hydrolases. Problems arising from the limited solubility of glycosyl ceramides in aqueous media were overcome by coating the substrate on a filter paper disc that had been treated with phosphatidyl choline. A comparison between the disc method and conventional dispersion of the substrate by detergents was made with two enzymes, galactosylgalactosyl-glucosyl ceramide galactosyl hydrolase (trihexosyl ceramide galactosyl hydrolase) from lysosomes of human and rat small intestine and human spleen, and d-galactose oxidase. In both cases enzymatic activity was greater with the paper disc method than it was with substrates dispersed by detergents. The galactose liberated by the glycosyl hydrolase was determined as the trimethylsilyl derivative of the free sugar by gas-liquid chromatography.

Alcohol Oxidoreductases↗
PubMed1968

Investigations on the oligosaccharide units of an A myeloma globulin.

The carbohydrate content of an A myeloma globulin was investigated. The carbohydrate content was found to be unchanged when the protein was isolated from the patient over a period of 18 months. The various polymeric forms of the protein contained similar proportions of carbohydrate. The A myeloma globulin contained approx. 2 residues of 6-deoxy-l-galactose (l-fucose), 14-15 of d-mannose, 12-13 of d-galactose, 12-13 of 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine), 6 of 2-acetamido-2-deoxy-d-galactose (N-acetyl-d-galactosamine) and 5 of N-acetylneuraminic acid (sialic acid), and these were distributed between six oligosaccharide units all of which were present on the heavy polypeptide chains. The oligosaccharide units showed two kinds of heterogeneity, which have been termed central and peripheral. Central heterogeneity was shown by the presence of three completely different core units, which had the following compositions: (1) 3 residues of d-galactose and 3 of 2-acetamido-2-deoxy-d-galactose, joined to protein by an O-glycosidic linkage between acetamidohexose and serine; (2) 3 residues of d-mannose, 2 of d-galactose and 3 of 2-acetamido-2-deoxy-d-glucose, joined to protein by an N-glycosidic linkage between acetamidohexose and aspartic acid; (3) 4 residues of d-mannose and 3 of 2-acetamido-2-deoxy-d-glucose with a linkage similar to that in (2). The core oligosaccharide units showed peripheral heterogeneity in the attachment of 6-deoxy-l-galactose, 2-acetamido-2-deoxy-d-glucose and N-acetylneuraminic acid. Tentative structures are proposed for these various types of oligosaccharide unit. Glycopeptides were isolated in which the sialic acid content exceeded that of d-galactose. Explanations are given for the electrophoretic mobility and staining characteristics of the various glycopeptides.

Chemical Phenomena↗
PubMed1968

Studies on the glycopeptides isolated from the urinary protein in heavy-chain disease.

The urinary protein excreted in heavy-chain disease was separated by ion-exchange chromatography into two broad fractions designated Cra-1 and Cra-2. For a dimeric molecular weight of approx. 51000, Cra-1 contained 3-4 residues of 6-deoxy-l-galactose (l-fucose), 10 of d-mannose, 5-6 of d-galactose, 12 of 2-acetamido-2-deoxy-d-glucose (N-acetyl-d-glucosamine) and 4-5 of N-acetylneuraminic acid (sialic acid), whereas the corresponding values for Cra-2 were 2, 10, 7, 12 and 7. Cra-2 contained in addition 1 residue of 2-acetamido-2-deoxy-d-galactose (N-acetyl-d-galactosamine). Cra-1 contained an average of four oligosaccharide units, two of which contained 1 residue of 6-deoxy-l-galactose, 3 of d-mannose, 1 of d-galactose and 3 of 2-acetamido-2-deoxy-d-glucose, whereas the other two units contained the same proportions of 6-deoxy-l-galactose, d-mannose and 2-acetamido-2-deoxy-d-glucose but 2 residues of d-galactose and 2 of N-acetylneuraminic acid. Cra-2 also contained an average of four oligosaccharide units, but the range of glycopeptides was much wider, containing 0-1 residue of 6-deoxy-l-galactose, 2-3 of d-mannose, 2-3 of d-galactose, 2-3 of 2-acetamido-2-deoxy-d-glucose and 1-3 of N-acetylneuraminic acid. Possible reasons for this heterogeneity are discussed. Glycopeptides were also isolated from Cra-2 that contained 1 residue of d-mannose, 2 of d-galactose, 1 of 2-acetamido-2-deoxy-d-galactose and 0-3 of N-acetylneuraminic acid.

Chromatography, Ion Exchange↗
PubMedDate not supplied

Mitochondrial abnormalities in CLN2 and CLN3 forms of Batten disease.

The storage of subunit c of mitochondrial ATP synthase, other hydrophobic peptides, and autofluorescent pigment in both late infantile (CLN2) and juvenile (CLN3) neuronal ceroid lipofuscinosis, but not in infantile (CLN1), has raised the question of abnormal mitochondrial function. We now report a partial deficiency in three types of fatty acid oxidation in intact skin fibroblasts from CLN2 and CLN3 patients, but not CLN1. We observed a statistically significant 33% reduction in palmitate (beta-oxidation; mainly mitochondrial) and lignocerate (beta-oxidation; mainly peroxisomal), and a 50% reduction in phytanic acid (alpha-oxidation; mainly peroxisomal) in the absence of exogenous carnitine. In contrast, when we measured fatty acid beta-oxidation (lignoceric acid and palmitic acid), in the same human skin fibroblasts, following lysis in the presence of carnitine, we found no difference in enzyme activity among normal, CLN1, CLN2, and CLN3. However, we did observe a 40% reduction in peroxisomal particulate (bound) catalase activity in CLN1 and CLN2 fibroblasts, which typically results from organellar lipid accumulation or a membrane abnormality. However, total catalase levels were normal, and Western blot analysis of this and three other major oxidant protective enzymes (Mn-dependent superoxide dismutase [MnSOD], CuZn-dependent superoxide dismutase [CuZnSOD], and glutathione peroxidase) were normal in CLN1, CLN2, and CLN3, as well as in liver from an animal (English Setter dog) model for CLN, which shows similar pathology and subunit c storage. Our data showing differences between CLN1 and forms CLN2 and CLN3 suggest some type of mitochondrial membrane abnormality as the source of the pathology in CLN2 and CLN3.

Animals↗
PubMedDate not supplied

Delta and sigma sites of clonal NCB20 cells do not modulate calcium uptake.

Opiate alkaloids and peptides are reported to inhibit 45Ca2+ binding to synaptic plasma membranes and uptake into brain synaptosomes. We have examined the effects of a number of opiates on 45Ca2+ uptake in a clonal cell line NCB20 which expresses multiple opioid binding sites. The cells express voltage-dependent calcium channels that are blocked by verapamil and nifedipine. In contrast to brain, 45Ca2+ uptake in these cells, in normal or high potassium medium, is unaffected by opiates. This difference may be due to the particular receptor types; the delta and sigma sites of these cells do not inhibit 45Ca2+ uptake.

Animals↗
PubMedDate not supplied

Mechanisms of apoptosis in embryonic cortical neurons (E6 and E7) in culture involve lipid signalling, protein phosphorylation and caspase activation.

Cultured embryonic (E7) chick neurons, derived from cerebral hemispheres, underwent apoptosis in response to inhibitors of protein kinase C (staurosporine) and phosphatidylinositol-3-kinase (wortmannin and LY294002), in a dose- and time-dependent manner. This was monitored by loss of cell viability, increased DNA fragmentation, and activation of caspase-3-like activity, all of which were partially reversed by elevating the level of cAMP in the cells with Bt(2)cAMP or (Sp)cAMPS. Further studies revealed that an early step in apoptosis was the formation of ceramide from sphingomyelin, resulting from the activation of a neutral pH sphingomyelinase activity. Thus inhibitors of protein kinase C and phosphatidylinositol-3-kinase increased ceramide levels in the same time-frame as caspase-3 activation and DNA fragmentation. Neurons could also be killed by the addition of either water-soluble C2-ceramide (30 microM) or natural C22/24 ceramide (0.5 microM). In contrast to the apparent protective effect of ser/thr protein phosphorylation, a pro-apoptotic role for tyrosine phosphate phosphorylation was suggested by the ability of protein tyrosine phosphate phosphatase inhibitor, Bis(maltolato)oxovanadium (IV) (BMOV), to induce apoptosis in E7CH neurons. Thus BMOV (25 microM) killed 50% of E7CH neurons and B lymphocytes but not glial cells, or T-lymphocytes, suggesting the existence of a common apoptotic pathway in neurons and B-cells. We conclude that the major pathway for programmed cell death in embryonic chick neurons has many elements in common with that described for other cells but that there may be some unique aspects which can be used to protect embryonic neurons from opioid and other drug-enhanced apoptosis.

Androstadienes↗
PubMedDate not supplied

Infants of depressed mothers exhibit atypical frontal electrical brain activity during interactions with mother and with a familiar, nondepressed adult.

Previous studies have shown that infants of depressed mothers exhibit atypical frontal brain electrical activity when they are interacting with their mothers. Whereas typically developing infants exhibit greater left versus right frontal brain activity, infants of depressed mothers have been found to exhibit reduced relative left frontal activity. The left frontal brain region has been associated with the expression of positive emotions. In the present study, the question of whether the atypical pattern of brain activity found in infants of depressed mothers generalizes to situations not involving mother was addressed. Brain electrical activity was recorded from 13- to 15-month-old infants of depressed (N = 59) versus nondepressed (N = 40) mothers during a baseline condition, and during several social conditions that included a playful social interaction with a familiar experiments. Infants of depressed mothers exhibited reduced left relative to right frontal activity during the baseline condition, and during interactions with their mothers and with the familiar experimenter. The present results suggest that the atypical pattern of electrical brain activity found in infants of depressed mothers generalizes to a variety of situations, including positive interactions with nondepressed adults.

Adult↗
PubMedDate not supplied

Correlation of circulating 17beta-oestradiol with haemostatic factors in healthy postmenopausal women.

The aim of the study was to evaluate any correlation between the circulating oestrogenic hormone 17beta-oestradiol and haemostatic factors in healthy postmenopausal women. In keeping with this objective, the correlations were evaluated irrespective of whether the source of the hormone was purely endogenous or exogenous as well. Accordingly, a univariate correlation adjusted for age, body mass index, and duration of menopause was determined in 42 healthy postmenopausal women aged 47-78 years, 19 of whom were self-reported users of hormone replacement therapy. The rest were self- reported never users. Serum 17beta-oestradiol exhibited a direct correlation with endogenous thrombin potential extrinsic pathway (R = 0.42, p = 0.01) and prothrombin fragments 1 and 2 (R = 0.37, p = 0.03) and an inverse correlation with antithrombin III (R = -0.36, p = 0.03) and alpha(2)-antiplasmin (R = -0.45, p = 0.005). The observations suggest an association of this hormone with net thrombin generation on the one hand and improved fibrinolysis on the other.

Adult↗
PubMedDate not supplied

Supplemental parenteral nutrition in cystic fibrosis.

The efficacy and safety of short-term supplemental peripheral hyperalimentation (PH) was evaluated in 15 hospitalized cystic fibrosis (CF) patients who exhibited varying degrees of pulmonary disease severity and nutritional impairment. An average of 1000 supplemental calories/day were administered intravenously for a 2- to 3-week period to patients being treated with parenteral antibiotics for exacerbation of their pulmonary disease. Eleven of 15 patients responded with a weight gain of greater than 2.0 kg and showed continued weight gain and stabilized pulmonary status for the 6- to 12-month follow-up period; two patients showed dramatic reversal of poor weight gain and growth following PH. Total calorie intake (oral + PH) equaled 141 +/- 40% of the recommended dietary allowances (RDA) in responders, with 45 +/- 12% RDA contributed by PH, in contrast to 68 +/- 20% of the RDA for total calories with 31 +/- 13% supplied using PH achieved in the nonresponders. Linoleic acid deficiency was documented in these patients (linoleic acid level as a percent of total fatty acid = 21.9% +/- 1.41 SEM vs 31.8% +/- 1.16 SEM in normal controls), and all seven patients achieved normalization of linoleic acid level after PH. Prior assessment of nutritional status (anthropometric measurements) or of severity of pulmonary disease (NIH clinical score) did not allow prediction of response to PH. No complications resulted from administration of PH to these hospitalized CF patients.

Adolescent↗