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PubMed1992

[The dawn or Somogyi phenomenon? High morning fasting blood sugar values in young type-1 diabetics].

High blood sugar levels in the morning in juvenile type 1 diabetics may be caused by a Somogyi phenomenon (counter-regulation after nocturnal hypoglycaemia) or insulin resistance in the morning hours (dawn phenomenon). To enable differentiation between the two, 1,562 blood sugar profiles (24 h, 3 h, 6 h) were determined in 161 children and juveniles (74 boys, 87 girls; mean age 10.8 [1.0-19.7] years) with type 1 diabetes mellitus. In accordance with the mechanism of the dawn phenomenon there was a close positive correlation between the blood sugar levels in the night and morning (r = +0.696; P less than 0.0001); the mean fasting blood sugar level was about 60 mg/dl above the 3 h value. Low nocturnal blood sugar levels as a possible cause of a high morning blood sugar (greater than 250 mg/dl) was demonstrated in fewer than 1% of profiles. On the other hand, the probability of nocturnal hypoglycaemia rose exponentially in the presence of low morning fasting blood sugar levels. Thus, if the morning level was below 80 mg/dl, the blood sugar levels at 3 h was below 50 mg/dl in 41.2%. This indicates that high morning blood sugar levels result from the dawn phenomenon and require a higher evening dose of slow-release insulin. But if the morning blood sugar values are clearly below 100 mg/dl, the cause may be nocturnal low blood sugar levels and the evening insulin dose should, therefore, be reduced.

Adolescent↗

PubMed2003

Refined sugar intake in Australian children.

OBJECTIVE: To estimate the intake of refined sugar in Australian children and adolescents, aged 2-18 years. DESIGN: Foods contributing to total sugar intake were identified using data from the National Nutrition Survey 1995 (NNS95), the most recent national dietary survey of the Australian population. The top 100 foods represented means of 85% (range 79-91%) and 82% (range 78-85%) of total sugar intake for boys and girls, respectively. Using published Australian food composition data (NUTTAB95), the proportion of total sugar being refined sugar was estimated for each food. Where published food composition data were not available, calculations from ingredients and manufacturer's information were used. SUBJECTS: The NNS95 assessed the dietary intake of a random sample of the Australian population, aged 2-18 years (n=3007). RESULTS: Mean daily intakes of refined sugar ranged from 26.9 to 78.3 g for 2-18-year-old girls, representing 6.6-14.8% of total energy intake. Corresponding figures for boys were 27.0 to 81.6 g and 8.0-14.0%, respectively. Of the 10 highest sources of refined sugar for each age group, sweetened beverages, especially cola-type beverages, were the most prominent. CONCLUSION: Refined sugar is an important contributor to dietary energy in Australian children. Sweetened beverages such as soft drinks and cordials were substantial sources of refined sugar and represent a potential target for campaigns to reduce refined sugar intake. Better access to information on the amounts of sugar added to processed food is essential for appropriate monitoring of this important energy source.

Adolescent↗

PubMed1994

Effects of high sugar diets on renal fluid, electrolyte and mineral handling in rats: relationship to blood pressure.

OBJECTIVE: We examined whether sugar-induced systolic blood pressure (SBP) elevations in rats may develop, in part, through a mechanism common to salt-induced hypertension, i.e., renal retention of water and salt. DESIGN: Spontaneously hypertensive rats (SHR) ate four diets: two high (> 50% of calories) and two low (< 12% of calories) in sugar (sucrose). SBP, various urinary parameters, and the renal angiotensin and prostaglandin systems were assessed. RESULTS: SHR consuming diets high in sugar showed significantly decreased urinary volume and excretion of electrolytes, which coincided with increasing SBP. When low sugar diets replaced high sugar diets, SBP and urinary parameters rapidly returned to baseline. SHR received captopril while consuming high sugar diets, and both SBP and urinary parameters assumed baseline values, comparable to ones seen in SHR consuming low sugar diets. A direct angiotensin II receptor antagonist (DuPont 753) did not influence SBP. However, we found decreased PGE2 excretion in SHR consuming excess sugar. CONCLUSIONS: Salt and water retention occur early during sugar-induced hypertension due to reduced renal excretion, consistent with some part in the pathogenesis. The effects of high sugar diets on SBP were not due to angiotensin II inhibition, however, decreased availability of vasodilatory prostaglandins may play a role in the renal events and sugar-induced hypertension in SHR.

Animals↗

PubMed1986

Effects of sugars on indices of glucose tolerance in humans.

Ten men and nine women were studied to determine whether replacement of utilizable complex carbohydrate by sugars (mono- and disaccharides) in a high-fiber, low-saturated fat diet would affect indices of glucose tolerance. Diets differed in that the 50% of calories derived from carbohydrate was either 35% complex and 15% sugars (low-sugar) on 15% complex and 35% sugars (high-sugar). Summation of glucose responses 30-180 min following an oral glucose tolerance test was significantly higher in men, but not women, after they consumed the high-sugar diet. Corresponding insulin responses were significantly higher in men consuming the high-sugar compared to the low-sugar diet. Insulin binding was significantly lower during the base line period and after the high-sugar diet compared to the low-sugar diet. Results indicate that sugars adversely affect indices of glucose tolerance when they replace complex carbohydrates even in a high-fiber, low-saturated fat diet.

Adult↗

PubMed2003

An in vivo experimental system to study sugar phloem unloading in ripening grape berries during water deficiency stress.

An in vivo experimental system-called the 'berry-cup' technique-was developed to study sugar phloem unloading and the accumulation of sugar in ripening grape berries. The berry-cup system consists of a single peeled grape berry immersed in a buffer solution in a cup prepared from a polypropylene syringe. A small cross-incision (2 mm in length) is made on the stylar remnant of a berry during its ripening phase, the skin of the berry then being easily peeled off, exposing the dorsal vascular bundles without damaging either these or the pulp tissue of the berry. The sites of sugar phloem unloading are thus made directly accessible and may be regulated by the buffer solution. In addition, the unloaded photoassimilates are easily transported into the buffer solution in the berry-cup. With the berry-cup technique, it takes 60 min to purge the sugar already present in the apoplast, after which the amount of sugar in the buffer solution is a direct measure of the sugar unloading from the grape berry phloem. The optimum times for sampling were 20 or 30 min, depending on the type of experiment. Sugar phloem unloading was significantly inhibited by the inclusion of either 7.5 mm NaF or 2.5 mm PCMB in the buffer solution. This study indicates that sugar phloem unloading in ripening grape berries is via the apoplastic network and that the process requires the input of energy. The system was shown to be an appropriate experimental system with which to study sugar phloem unloading in ripening grape berries, and was applied successfully to the study of berry sugar unloaded from grapevines subjected to water stress. The results showed that water deficiency inhibits sugar unloading in grape berries.

Carbohydrate Metabolism↗

PubMed1996

Effects of sugar availability on the blood-feeding behavior of Anopheles gambiae (Diptera:Culicidae).

Blood-feeding behavior and survivorship of individual Anopheles gambiae Giles females were observed daily in cohorts with either access to sugar (n = 76) or without sugar (n = 80). Individual mosquitoes were allowed to feed daily on an anesthetized mouse. Mosquitoes provided with sugar lived on average almost 3 d longer than females without sugar (19.0 versus 16.2 d). After stratification by age, mosquitoes in the youngest (5-12 d) and middle (13-19 d) age strata showed no differences in blood-feeding patterns relative to sugar availability. However, mosquitoes from the oldest age group and no access to sugar had more total blood feeds than long-lived females ( > or = 20 d) with access to sugar (9.8 versus 6.5). Furthermore, mosquitoes > or = 20 d old and without sugar available had a higher blood-feeding frequency than females that had sugar available (0.36 versus 0.25 blood meals per female per day). The enhanced blood-feeding capability among older sugar-deprived An. gambiae emphasized the close association between sugar-feeding and blood-feeding behavior and the potential consequences for the transmission of malaria parasites and other pathogens.

Animals↗

PubMed1993

Structures of sugar chains of hen egg yolk riboflavin-binding protein.

The structures of the sugar chains of hen yolk riboflavin-binding protein (RBP) were established. Asparagine-linked sugar chains of yolk-RBP were liberated by hydrazinolysis. Free amino groups of the sugar chains were acetylated and the reducing-end sugar residues were tagged with 2-aminopyridine. Fluorescent pyridylamino (PA-) derivatives of the sugar chains were purified by gel-filtration and reversed-phase HPLC. Seven PA-sugar chains were isolated, and the structure of each was determined by composition analysis, sequential exoglycosidase digestion, methylation analysis, and 500-mHz 1H-NMR spectroscopy. These analyses showed that the main sugar chains had sialylbiantenna and sialyltriantenna structures. PA-sugar chains of plasma-RBP were also isolated, and the structures of the PA-sugar chains of yolk- and plasma-RBPs were compared as to their elution patterns on anion-exchange chromatography and reversed-phase HPLC. The plasma RBP had almost the same sugar chains as the yolk RBP did, indicating that sugar chains are not modified during incorporation into the oocyte.

Animals↗

PubMed1996

Sugar regulation of harvest-related genes in asparagus.

The signals controlling the abundance of transcripts up-regulated (pTIP27, pTIP31, and pTIP32) or down-regulated (pTIP20 and pTIP21) after harvest in asparagus (Asparagus officinalis L.) spears were examined. pTIP27 and pTIP31 are known to encode asparagine synthetase (AS) and a beta-galactosidase (beta-gal) homolog, respectively. The nucleotide sequences of pTIP20, pTIP21, and pTIP32 were determined, and they encode histone 3, histone 2B, and an unknown product, respectively. Changes in respiration, soluble sugars, and abundance of the five mRNAs were similar in the tips stored as 30-mm lengths or as part of 180-mm spears. We previously hypothesized that sugars may regulate the level of AS transcripts in asparagus tissue. Asparagus cell cultures were used to test the role of sugar status may regulate the level of AS transcripts in asparagus tissue. Asparagus cell cultures were used to test the role of sugar status in regulating gene expression. Transcript abundance for AS, beta-gal, and pTIP32 was low in cells in sugar-containing medium but increased within 12 h after transferring cells to a sugar-free medium. Histone 3 and histone 2B transcripts were, in general, abundant in cells on sugar-containing medium but declined in abundance when transferred to sugar-free medium. When cells were returned to sugar-containing medium the abundance of transcripts for histone 3 and histone 2B increased, whereas that for AS, beta-gal, and pTIP32 decreased. Soluble sugar levels are known to decline rapidly in the tips of harvested spears. Metabolic regulation by sugar status may have a major influence on gene expression in asparagus spears and other tissue after harvest.

Aspartate-Ammonia Ligase↗

PubMed2000

Multiple signaling pathways in gene expression during sugar starvation. Pharmacological analysis of din gene expression in suspension-cultured cells of Arabidopsis.

We have identified many dark-inducible (din) genes that are expressed in Arabidopsis leaves kept in the dark. In the present study we addressed the question of how plant cells sense the depletion of sugars, and how sugar starvation triggers din gene expression in suspension-cultured cells of Arabidopsis. Depletion of sucrose in the medium triggered marked accumulation of din transcripts. Suppression of din gene expression by 2-deoxy-Glc, and a non-suppressive effect exerted by 3-O-methyl-Glc, suggested that sugar-repressible expression of din genes is mediated through the phosphorylation of hexose by hexokinase, as exemplified in the repression of photosynthetic genes by sugars. We have further shown that the signaling triggered by sugar starvation involves protein phosphorylation and dephosphorylation events, and have provided the first evidence that multiple pathways of protein dephosphorylation exist in sugar starvation-induced gene expression. An inhibitor of serine/threonine protein kinase, K-252a, inhibited din gene expression in sugar-depleted cells. Okadaic acid, which may preferentially inhibit type 2A protein phosphatases over type 1, enhanced the transcript levels of all din genes, except din6 and din10, under sugar starvation. Conversely, a more potent inhibitor of type 1 and 2A protein phosphatases, calyculin A, increased transcripts from din2 and din9, but decreased those from other din genes, in sugar-depleted cells. On the other hand, calyculin A, but not okadaic acid, completely inhibited the gene expression of chlorophyll a/b-binding protein under sugar starvation. These results indicate that multiple signaling pathways, mediated by different types of protein phosphatases, regulate gene expression during sugar starvation.

Arabidopsis↗

PubMed1990

Sugar uptake and starch biosynthesis by slices of developing maize endosperm.

(14)C-Sugar uptake and incorporation into starch by slices of developing maize (Zea mays L.) endosperm were examined and compared with sugar uptake by maize endosperm-derived suspension cultures. Rates of sucrose, fructose, and d- and l-glucose uptake by slices were similar, whereas uptake rates for these sugars differed greatly in suspension cultures. Concentration dependence of sucrose, fructose, and d-glucose uptake was biphasic (consisting of linear plus saturable components) with suspension cultures but linear with slices. These and other differences suggest that endosperm slices are freely permeable to sugars. After diffusion into the slices, sugars were metabolized and incorporated into starch. Starch synthesis, but not sugar accumulation, was greatly reduced by 2.5 millimolar p-chloromercuribenzenesulfonic acid and 0.1 millimolar carbonyl cyanide m-chlorophenylhydrazone. Starch synthesis was dependent on kernel age and incubation temperature, but not on external pH (5 through 8). Competing sugars generally did not affect the distribution of (14)C among the soluble sugars extracted from endosperm slices incubated in (14)C-sugars. Competing hexoses reduced the incorporation of (14)C into starch, but competing sucrose did not, suggesting that sucrose is not a necessary intermediate in starch biosynthesis. The bidirectional permeability of endosperm slices to sugars makes the characterization of sugar transport into endosperm slices impossible, however the model system is useful for experiments dealing with starch biosynthesis which occurs in the metabolically active tissue.

Journal Article↗

PubMed2006

Heat sensitivity of photosynthetic electron transport varies during the day due to changes in sugars and osmotic potential.

In water-stressed leaves, accumulation of neutral osmotica enhances the heat tolerance of photosynthetic electron transport. There are large diurnal and day-to-day changes in leaf sugar content because of variations in net photosynthetic production, respiration and retranslocation. To test the hypothesis that diurnal and day-to-day variations in leaf sugar content and osmotic potential significantly modify the responses to temperature of photosynthetic electron transport rate, we studied chlorophyll fluorescence rise temperatures (i.e. critical temperatures at break-points in fluorescence versus temperature response curves, corresponding to enhanced damage of PSII centers and detachment of pigment-binding complexes) in the dark at a background of weak far-red light (T(FR)) and under actinic light (T(L)), and responses of foliar photosynthetic electron transport rate to temperature using gas-exchange and chlorophyll fluorescence techniques in the temperate tree Populus tremula L. Sucrose and sorbitol feeding experiments demonstrated strong increases of fluorescence rise temperatures T(FR) and T(L) with decreasing leaf osmotic potential and increasing internal sugar concentration. Similar T(FR) and T(L) changes were observed in response to natural variation in leaf sugar concentration throughout the day. Increases in leaf sugar concentration led to an overall down-regulation of the rate of photosynthetic electron transport (J), but increases in the optimum temperature (Topt) of J. For the entire dataset, Topt varied from 33.8 degrees C to 43 degrees C due to natural variation in sugars and from 33.8 degrees C to 52.6 degrees C in the sugar feeding experiments, underscoring the importance of sugars in modifying the response of J to temperature. However, the correlations between the sugar concentration and fluorescence rise temperature varied between the days. This variation in fluorescence rise temperature was best explained by the average temperature of the preceding 5 or 6 days. In addition, there was a significant year-to-year variation in heat sensitivity of photosynthetic electron transport that was associated with year-to-year differences in endogenous sugar content. Our data demonstrate a diurnal variation in leaf heat tolerance due to changes in sugar concentration, but they also show that this short-term modification in heat tolerance is super-imposed by long-term changes in heat resistance driven by average temperature of preceding days.

Carbohydrate Metabolism↗

PubMed2001

Voltammetric detection of lectin using sugar labeled with electroactive substance.

The voltammetric detection of soybean agglutinin (SBA) was investigated on the basis of an interaction between the lectin and a sugar. Because galactose and lactose combined with SBA, the sugars were labeled by a Schiff base with an electroactive daunomycin. After the labeled sugar and SBA were mixed, measurements were carried out by voltammetry. When SBA-sugar binding occurs, a part of daunomycin of the labeled sugar is taken to the binding sites. As a result, SBA is detected by a change in the peak current of daunomycin, and the SBA-sugar interaction is evaluated. The length of the alkyl chain between daunomycin and the sugar was also considered. The electrode response to the concentration of SBA was linear over the range of 0.04-0.8 microg min(-1). The merits of this procedure are the convenient preparation of labeled sugar and a rapid measurement without separation. On the other hand, the detection of sugar at the 10(-9) mol dm(-3) level was achieved by a competitive reaction to limited binding sites of the lectin between the sugar and the labeled sugar.

Carbohydrates↗

PubMed1981

Contents and compositions of the aroma in "Wasanbon" sugar.

"Wasanbon" sugar is handmade sugar which has been manufactured traditionally in Japan by a unique refining procedure, and is used in the making of Japanese traditional confectionary. No reports have been published on the substances responsible for the unique aroma of "Wasabon" sugar. In this paper, the contents and compositions of the aroma in "Wasabon" sugar and refinery final molasses are reported as studied by column chromatography, gas chromatography, mass spectrometry and sensory evaluation. The samples are the first press-off molasses ("Ara-mitsu" molasses) refinery final molasses, "Shiroshita" sugar (prerefined sugar) and "Wasabon" sugar. The summarized results are as follows: In the acidic fraction, the aroma of 3-phenylpropionic acid is similar to the stored aroma of "Wasabon" sugar, whereas the aroma of its methyl ester was not similar to that aroma. Although aroma contents of the weakly acidic fraction in "Wasabon" sugar and refinery final molasses are 8.5 to 8.7% of those of the acidic fraction, and their main components are cyclotene and maltol, which are formed by thermal degradation of sugar. These components show a higher preference than other weakly acidic fraction aromas, by a paired preference test. Cyclotene and maltol increased about 3.7 and 1.5 times, respectively, by the heating of "Shiroshita" sugar.

Candy↗

PubMedDate not supplied

Sugar content of commonly eaten snack foods of school children in relation to their dental health status.

Sugar is the principal substrate for micro-organisms causing dental caries. Yet it is impossible to eliminate sugar in the diet as almost all available foods particularly snack foods contain sugar. WHO recommended 10 kg. sugar or 27.40 gms. per person per year in non-fluoridated area and 15 kg. sugar/person year in non-flouridated areas for low caries prevalence. The FFQ and 24-Hour Food recall of 824 rural and urban schoolchildren showed that all their snacks foods are high in sugar except gelatine. Their sugar intake was three times more than the WHO recommendation with a mean daily intake of 90 gms. for urban and 88 grams of sugar for the rural. White sugar, hard candies, raisins, coco jam, and milk choco were the five most commonly eaten snack foods with high sugar content. Oral examination of the schoolchildren showed that dental caries was higher in the urban than in the rural. As a whole, the urban schoolchildren consumed more sugar and had higher dental caries compared to the rural schoolchildren. No significant correlation was found between sugar intake and dental caries.

Adolescent↗

PubMed2003

Rheumatic disease differentiation using immunoglobulin G sugar printing by high density electrophoresis.

OBJECTIVE: To determine whether immunoglobulin G (IgG) sugar printing using high density electrophoresis can be a diagnostic and prognostic test to rapidly differentiate early rheumatoid arthritis (ERA), rheumatoid arthritis (RA), and other rheumatic diseases from each other. METHODS: One hundred fifty-three patients with ERA/RA, psoriatic arthritis (PsA), early psoriatic arthritis (EPsA) ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), early undifferentiated seronegative arthritis (UA), and osteoarthritis (OA) were investigated. Samples of their serum IgG were purified, and sugars were released enzymatically and fluorophore-labelled, then subjected to high density electrophoresis, and relative quantities of each sugar were determined by optical density. RESULTS: Sugar prints of 9 sugars were compiled for each of the 9 disease groups. Specific disease-associated sugar changes were determined by comparison with OA. For example, agalactosylated structures were increased in ERA/RA and EPsA/PsA (p = 0.0001-0.004) and digalactosylated structures were decreased in PsA, AS, and JIA (p = 0.0001-0.04). When the disease groups were compared, each disease was characterized by a unique sugar print comprising 7 of the 9 sugars (p = 0.001-0.005); only g0fb and a1f were not associated. ERA/RA differed in the quantities of monogalactosyl and sialylated sugars (p = 0.006-0.007). The presence of agalactosyl sugars enabled correct prediction of RA in 71.2% of individuals, with a specificity of 84.2% and sensitivity of 50.0%. The area under the sensitivity versus specificity curve was 0.7812. CONCLUSION: IgG sugar printing was found to be effective in differentiation of rheumatic diseases and can differentiate ERA and RA from each other and from other rheumatic diseases; and hence may constitute a relatively rapid diagnostic and prognostic test for patients presenting with arthritis.

Adult↗

PubMed2006

[Regularity of sugar-uptake in human red blood cells].

Lyophilization of human red blood cells has important significance in clinical application. Some sugars, especially trehalose, can be more tolerant of some organism or cells to dry environments, But, how to bring sugars into cells is a challenge. This study was aimed to investigate the regularity of sugar-uptake in human red blood cells. The absorption rate of trehalose and glucose in red blood cells, free hemoglobin level and erythrocyte deformation index were determined at different incubation temperature (4, 25 and 37 degrees C), different sugar concentration (0, 0.2, 0.4, 0.6, 0.8 and 1 mol/L) and different incubation time (1, 3, 5, 7 and 9 hours). The results showed that with increase of temperature and extracellular sugar concentration, the uptake of sugar in red blood cells also increased, the intracellular trehalose and glucose concentrations were over 30 mmol/L and 40 mmol/L respectively. The effects of incubation time on uptake of trehalose and glucose were different. With prolonging of incubation time, the uptake of trehalose showed firstly increase and then decrease, however, the uptake of glucose showed a constant increase. But the loading process had side-effect on free hemoglobin and maximum deformation index (MAXDI) of red blood cells, especially for trehalose, which mainly come from high osmotic pressure. It is concluded that the uptake of sugars in red blood cells is closely dependent on incubation temperature, extracellular sugar concentration and incubation time. In certain condition, the efficiency of sugar uptake is very high, but this process also damages red blood cells so as to affect the application of sugars in lyophilization of red blood cells. The research in the future should focus on how to deal with the relation between cell injury and uptake efficiency of sugar in red blood cells.

Blood Preservation↗

PubMed1987

A model for accelerated uptake and accumulation of sugars arising from phosphorylation at the inner surface of the cell membrane.

A model transport system for cellular accumulation of sugar coupled to phosphorylation is described. Sugar permeates the cell membrane via a passive facilitated transport system. On the inside surface of the membrane the bound sugar is either phosphorylated to form impermeable hexose phosphate, which is released into the intracellular solution, or released directly into the cytosol. Sugar may be regenerated from hexose phosphate in the cytosol via a phosphatase reaction. The reduction of the proportion of sites on the inner membrane surface occupied by permeable sugar, caused by the kinase reaction, increases both net and unidirectional passive inflow and reduces both net and unidirectional exit of sugar, thereby permitting large stationary state gradients of free sugar to be maintained between the cytosol and bathing solution. In cells where there is a high passive membrane permeability to free sugar, steady-state accumulation of free sugar within the cytosol, linked to metabolism is inexplicable in terms of conventional transport kinetics based on equilibrium thermodynamic assumptions. This phenomenon is analysed in terms of non-equilibrium stationary state flows of ligands via a probability network. The effects of metabolism on exchange transport are also examined. The model provides a framework to explain how sugar transport is loosely coupled to phosphorylation in mammalian epithelial cells, adipocytes, yeasts and bacteria, so that a high rate of substrate accumulation is maintained without requiring a reduction in the intracellular concentration of permeable substrate below that in the external solution.

Adenosine Triphosphate↗

PubMed1983

The effect of unphosphorylated and phosphorylated sugar moieties on human and mouse natural killer cell activity: is there selective inhibition at the level of target recognition and lytic acceptor site?

A number of different sugars were investigated for their effect on human and mouse natural killer cell (NK)-mediated cytolysis. From the pool of nonphosphorylated sugars, D-mannose, N-acetyl-D-glucosamine (NAcGlc), D-glucose, and, to a lesser extent, beta-gentiobiose were found to inhibit human NK cytolysis. Mouse NK activity against YAC-1 target cells was reduced consistently in the presence of D-mannose and NAcGlc only. The sugars, NAcGlc, D-glucose, and beta-gentiobiose, were specifically inhibitory against NK-mediated cytolysis with no inhibitory effects being observed against ADCC, monocyte-mediated cytolysis, or CTL activity. Pretreatment and washing at either the target or effector cell level as well as direct target binding assays using Percoll-purified NK cells indicated that at least NAcGlc and beta-gentiobiose function at the recognition stage of NK cytolysis. D-Mannose, which was the most effective nonphosphorylated sugar inhibitor, was capable of inhibiting all cell-mediated cytotoxic mechanisms tested (NK, ADCC, monocyte, and CTL) and its action did not appear to be solely due to an impairment in the recognition event. All the phosphorylated sugars caused significant inhibition of human and mouse NK-mediated cytolysis, although repeated analyses of sugar titration curves consistently showed mannose-6-phosphate (Man-6-P) to be the most effective inhibitor. Inhibition with the phosphorylated sugars was apparent against all cytotoxic mechanisms investigated. It is possible that these sugars may function as general metabolic inhibitors or may activate a common signal which negatively regulates cell-mediated cytotoxic mechanisms. Nevertheless, the relative degree of inhibition with the majority of these sugars (particularly Man-6-P) was greater against NK and ADCC activity than against monocyte and CTL activity. Furthermore, studies with selected well-characterized human and mouse NK-resistant target cells strongly indicated that these sugars, particularly Man-6-P, compete at an acceptor site responsible for the uptake of the NK lytic factor, which is independent of the recognition structure(s).

Animals↗