Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GALACTOSE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1969

Radioautographic visualization of the incorporation of galactose-3H and mannose-3H by rat thyroids in vitro in relation to the stages of thyroglobulin synthesis.

Rat thyroid lobes incubated with mannose-(3)H, galactose-(3)H, or leucine-(3)H, were studied by radioautography. With leucine-(3)H and mannose-(3)H, the grain reaction observed in the light microscope is distributed diffusely over the cells at 5 min, with no reaction over the colloid. Later, the grains are concentrated towards the apex, and colloid reactions begin to appear by 2 hr. With galactose-(3)H, the reaction at 5 min is again restricted to the cells but it consists of clumped grains next to the nucleus. Soon after, grains are concentrated at the cell apex and colloid reactions appear in some follicles as early as 30 min. Puromycin almost totally inhibits incorporation of leucine-(3)H and mannose-(3)H, but has no detectable effect on galactose-(3)H incorporation during the 1st hr. Quantitation of electron microscope radioautographs shows that mannose-(3)H label localizes initially in the rough endoplasmic reticulum, and by 1-2 hr much of this reaction is transferred to the Golgi apparatus. At 3 hr and subsequently, significant reactions are present over apical vesicles and colloid, while the Golgi reaction declines. Label associated with galactose-(3)H localizes initially in the Golgi apparatus and rapidly transfers to the apical vesicles, and then to the colloid. These findings indicate that mannose incorporation into thyroglobulin precursors occurs within the rough endoplasmic reticulum; these precursors then migrate to the Golgi apparatus, where galactose incorporation takes place. The glycoprotein thus formed migrates via the apical vesicles to the colloid.

Autoradiography↗
PubMed1997

Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175.

The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spirochroman-4-5'- imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a daily diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.

Aldehyde Reductase↗
PubMed1998

Diabetic-like corneal sensitivity loss in galactose-fed rats ameliorated with aldose reductase inhibitors.

This study investigated whether diabetic-like corneal sensory deficits occur in the galactose-fed rat model of diabetic ocular complications and if such deficits could be prevented using either of two structurally different aldose reductase (AR) inhibitors, CT-112 or AL-1576. S-D rats were randomly grouped to receive a diet of Purina chow with either 50% starch (n=25) or 50% D-galactose (n=65). Some of the galactosemic rats received either 0.25% CT-112 topically 3x daily (n=15) or 28 mg/kg body wt/day AL-1576 systemically (n=10). The control and untreated galactosemic rats in the CT-112 portion of the study received equivalent topical doses of the vehicle. Sensitivity measurements were made with a Cochet-Bonnet Aesthesiometer mounted on a micromanipulator. The filament was applied to the central corneal surface (mean pressure of 0.96 g/mm2) and viewed using a slit-lamp biomicroscope. Ten consecutive stimuli were conducted on each cornea and the average number of blink-responses was expressed as a percent of total stimuli effected. Mean initial corneal sensitivities were similar in all groups. Corneal sensitivity in the galactosemic rat was reduced (p<0.01) at each monthly measurement compared to control. Animals treated with CT-112 or AL-1576 showed a significant increase in the mean blink-response compared to untreated galactose-fed rats and did not differ significantly from controls towards the completion of the 7 month study. Animals treated with AL-1576 did not develop cataracts, whereas those treated topically with CT-112 and untreated galactose-fed rats developed bilateral nuclear cataracts within 3 weeks. This is the first study to demonstrate decreased corneal sensitivity in the galactose-fed rat model and its amelioration with AR inhibitors. Thus, aldose reductase, the first enzyme of the polyol pathway, may have an important role in the pathogenesis of decreased corneal sensitivity. The model could be useful for investigating the pathogenic mechanism(s) involved in reduced corneal sensitivity associated with diabetic keratopathy in humans.

Aldehyde Reductase↗
PubMed1998

Effect of aldose reductase inhibitor on corneal epithelial barrier function in galactose-fed dogs.

The effect of concomitant administration of galactose and the aldose reductase inhibitor(ARI) Epalrestat (Kinedak) on corneal barrier function was examined in dogs. Six-month-old male beagles were rendered aphakic in one eye and then divided into four groups as follows: 1) a control group fed on 30% cellulose, 2) a galactosemic group fed on 30% galactose, 3) a 30% galactose-fed group treated with low dose (20 mg/kg) ARI and 4) a 30% galactose-fed group treated with high dose (50 mg/kg) ARI. Forty-one months after the start of these diets, corneal autofluorescence and the corneal barrier function were measured in each dog using anterior fluorophotometry (FL-500). When barrier function was analyzed in non-operated eyes, fluorescence data were significantly higher in the galactosemic group compared to the control group. In non-operated eyes, fluorescent data in high-dose ARI treated group were significantly lower than those in the galactosemic group. However, in operated eyes, no significant difference was observed between the galactosemic group and the ARI treated groups. Similar trends were observed when corneal autofluorescence of each group was compared. Long-term galactose feeding appeared to damage corneal epithelial barrier function. This damage was not observed in the high-dose ARI treated group suggesting that this damage may be linked to the polyol pathway.

Aldehyde Reductase↗
PubMed1972

Isolation of plaque-forming, galactose-transducing strains of phage lambda.

Plaque-forming, galactose-transducing lambda strains have been isolated from lysogens in which bacterial genes have been removed from between the galactose operon and the prophage by deletion mutation.-A second class has been isolated starting with a lysogenic strain which carries a deletion of the genes to the right of the galactose operon and part of the prophage. This strain was lysogenized with a second lambda phage to yield a lysogen from which galactose-transducing, plaque-forming phages were obtained. These plaque-forming phages were found to be genetically unstable, due to a duplication of part of the lambda chromosome. The genetic instability of these partial diploid strains is due to homologous genetic recombindation between the two identical copies of the phage DNA comprising the duplication. The galactose operon and the duplication of phage DNA carried by these strains is located between the phage lambda P and Q genes.

Centrifugation, Density Gradient↗
PubMed1998

Molecular basis of recognition by Gal/GalNAc specific legume lectins: influence of Glu 129 on the specificity of peanut agglutinin (PNA) towards C2-substituents of galactose.

The ability to discriminate between galactose and N- acetylgalactosamine, observed in some lectins, is crucial for their biological activity as well as their usefulness as tools in biology and medicine. However, the molecular basis of differential binding of lectins to these two sugars is poorly understood. Peanut agglutinin (PNA) is one of the few galactose-specific legume lectins which does not bind N- acetylgalactosamine at all and is, therefore, ideal for the study of the basis of specificity towards C-2 substituted derivatives of galactopyranosides. Examination of the three-dimensional structure of PNA in complex with lactose revealed the presence of both a longer loop and bulkier residues in the region surrounding the C-2 hydroxyl of the galactopyranoside ring, which can sterically prevent the accommodation of a bulky substituent in this position. One such residue, is a glutamic acid at position 129 which protrudes into the binding site and perhaps directly obstructs any substitution at the C-2 position. Two mutants in bacterially expressed PNA were therefore constructed. These were E129D and E129A, in which Glu129 was replaced by Asp and Ala, respectively. The specificity of the mutants for galactose, galactosamine, and N- acetylgalactosamine was examined through observing the inhibition of hemagglutination and binding of the lectin to immobilized asialofetuin. The results showed that the affinity of E129A and E129D for C-2-substituted derivatives of the galactose varies. The mutant E129D showed significant binding towards N- acetylgalactosamine, suggesting that the residue Glu 129 is crucial in imparting exclusive galactose-specificity upon PNA. This study not only attempts to provide an explanation for the inability of PNA to accommodate C-2-substituted derivatives at its primary subsite, but also seeks to present a basis for engineering lectins with altered specificities.

Acetylgalactosamine↗
PubMed1993

Autoregulation of GAL4 transcription is essential for rapid growth of Kluyveromyces lactis on lactose and galactose.

Transcriptional induction of genes in the lactose-galactose regulon of the yeast Kluyveromyces lactis requires the GAL4 transcription activator protein. Previous data indicated that the concentration of GAL4 was tightly regulated under basal, inducing, and glucose repressing conditions but the mechanisms were unknown. In this paper we demonstrate that transcription of the GAL4 gene (KI-GAL4) increases 3- to 4-fold during induction of the regulon. This increase requires a KI-GAL4 binding site, UASG, in front of the KI-GAL4 gene, indicating that the KI-GAL4 protein autoregulates transcription of its own gene. Our data demonstrate that the autoregulatory circuit is essential for full induction of the lactose-galactose regulon and, hence, for rapid growth on lactose or galactose. Other data indicate that basal transcription of the KI-GAL4 gene is governed by unidentified promoter elements. The existence of the autoregulatory circuit reveals an important difference between the lactose-galactose regulon and its homologue in Saccharomyces cerevisiae, the melibiose-galactose regulon. This difference may have evolved in response to different selective pressures encountered by the two organisms.

Base Sequence↗
PubMed1986

Abnormal nerve regeneration in galactose neuropathy.

Nerve regeneration across a 10 mm gap through an implanted silicone tube was delayed in galactose-fed rats two and four weeks after transecting the nerve. This experimental metabolic neuropathy resembles diabetic neuropathy in which nerve regeneration is also delayed. Experiments were performed by introducing opposite ends of divided sciatic nerves into close-fitting silicone tubes, leaving a 10 mm gap. Growth of neurites across this gap was monitored by electron microscopy performed in sections at regular intervals of 2 mm from proximal to distal stumps. After two weeks some difference was apparent; axons advanced 1.4 +/- 0.4 mm in galactose-fed rats versus 3.5 +/- 1.5 mm in controls. Myelination did not progress beyond 1 mm in galactose-fed rats. Differences were greater between the two groups at four weeks. The growth of axons in galactose rats was 3.5 +/- 0.2 mm versus 9.4 +/- 0.1 mm in control nerves. In addition the size of the regenerating stump was much greater in control rats. Qualitative differences were also noticed during electron microscopic comparison of control and galactose-treated rats. The dystrophic axons seen in treated rats had abnormal electron-dense organelles, lamellated bodies, vesicles and tubular structures, as well as numerous glycogen granules. Abnormalities of spatial orientation were also noted. Unlike control axons which grew parallel with the long axis of the tube, regenerating axons in experimental animals were seen deviating from the axis at 90 degrees angles. Both immature sprouts and myelinating axons showed abnormal plasticity. Ultrastructural differences were also noted in Schwann cells, macrophages and vessels.

Animals↗
PubMed2005

Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies.

Ovarian cancer is the fifth most common cause of cancer death among women and the leading cause of gynaecological cancer death in the United States. Milk/dairy products consumption was considered to be a risk factor for ovarian cancer mainly because milk carbohydrate-lactose and galactose metabolism is toxic to oocytes. However, recent evidence does not support this hypothesis completely. We collected epidemiological studies related to the association between milk/dairy products consumption or galactose metabolism (lactose, galactose, galactose-1-phosphate uridyltransferase, lactose/transferase) and ovarian cancer published between January 1966 and August 2003 and found 27 items from 22 independent studies. Twenty studies were case-control studies and the other two were cohort studies. A meta-analysis method was conducted to estimate relative risk combining all relative data. In general, we did not find any association between milk/dairy products or galactose metabolism and ovarian cancer risk in this meta-analysis. The consumption of whole milk and butter, which contain relatively high amounts of fat, was positively (relative risk > 1.2), but not significantly, associated with an increased risk.

Case-Control Studies↗
PubMed1978

Galactose-1-phosphate accumulation by a Duarte-transferase deficiency double heterozygote.

An infant, suspected of having galactosemia following a positive screening test on dried blood spots, was shown to be a Duarte-transferase deficiency compound heterozygote through studies of electrophoretic mobility of the transferase enzyme in blood from the patient and family members. No rise in blood glucose was seen following oral ingestion of galactose. At the same time, galactose rose in plasma and was excreted in the urine; galactose-1-phosphate accumulated in erythrocytes. A galactose-free diet was considered the prudent course in the presence of the patient's inability to metabolize galactose completely.

Blood Glucose↗
PubMed1981

Experimental galactose toxicity: effects on synaptosomal phosphatidylinositol metabolism.

Experimental galactose toxicity was induced by weaning rats onto an isocaloric 40% galactose diet. Synaptosomes were prepared from cerebra of rats at 2-9 weeks post-weaning and incubated with [33P][i and myo-[2-3H]inositol in the presence or absence of 0.2 mM-acetylcholine. The acetylcholine-stimulated [33P]Pi labeling of phosphatidylinositol and the changes in amounts of phosphatidylinositol were similar in the normal and galactose-toxic rats; however, acetylcholine-stimulated myo-[2-3H]inositol labeling of phosphatidylinositol was markedly decreased in the galactose-toxic rats. The impairment of acetylcholine-stimulated myo-[2-3H]inositol incorporation into phosphatidylinositol observed after 2 weeks on the diet did not vary after more prolonged exposure to galactose.

Acetylcholine↗
PubMed1986

The effect of physiological temperature changes on the galactose elimination capacity of the isolated perfused pig liver.

The effect of temperature changes (36-40 degrees C) on the liver function was studied in the isolated perfused pig liver. When compared with control studies no effect was observed on lactate, glucose, bile flow, ATP and energy charge, and the recovery after the changes in temperature was complete. The only significant changes observed regarded the hepatic oxygen uptake and galactose elimination capacity. The increase of 1 degree C resulted in an increase in galactose elimination of 6%, corresponding to a Q10 of 1.98 (SEM 0.12) with an energy of activation of 48 kJ/mol (SEM 4.7). Oxygen uptake was linearly related to galactose elimination (1.75 mol for 1 mole change in galactose elimination). These results indicate that circulatory changes are unimportant within physiological temperature changes. It is concluded that temperature effects on galactose elimination are too small to warrant a correction when used as a clinical test of quantitative liver function.

Adenosine Diphosphate↗
PubMed1986

D-galactose transport in rat intestinal brush border membrane vesicles studied with a molecular-sieve technique.

A technique using G-50 Sephadex molecular-sieve chromatography has been developed to study both the accumulation of transported solutes by rat intestinal brush border membrane vesicles and the wash-out of these solutes from pre-loaded vesicles. The extent to which D-galactose was taken up into the brush border membrane vesicles was dependent on the medium osmolarity and this dependence was significantly reduced (P less than 0.01) by pre-treating the vesicles with the non-ionic detergent Triton X-100. The transport of D-galactose into the brush border membrane vesicles was sodium dependent, electrogenic and phloridzin sensitive. It is, therefore, qualitatively similar to D-glucose transport into brush border membrane vesicles. The wash-out of D-galactose from pre-loaded brush border membrane vesicles was inhibited by phloridzin and accelerated by the presence of an outwardly directed sodium gradient. D-Galactose was released from the pre-loaded brush border membrane vesicles more slowly than D-glucose and this difference was consistent with the higher overshoot found for D-galactose during the transport of the sugars into the vesicles.

Animals↗
PubMed1979

Galactosemia: alterations in sulfate metabolism secondary to galactose-1-phosphate uridyltransferase deficiency.

Cultures of nonmutant as well as galactokinase-deficient fibroblasts incorporate 20 percent more [35S]sulfate when galactose is substituted for glucose in the medium; galactose-1-phosphate uridyltransferase-deficient cells incorporate 65.5 percent less. In addition to incorporating less [35S]sulfate, the uridyltransferase-deficient cells showed significant accumulation of intracellular galactose-1-phosphate within 4 hours after galactose exposure. Under the same conditions, no difference in [3H]uridine incorporation was observed. This metabolic alteration, occurring in response to galactose exposure, may be related to the pathophysiology of classical galactosemia.

Cells, Cultured↗
PubMed2005

Improvement of galactose uptake in Saccharomyces cerevisiae through overexpression of phosphoglucomutase: example of transcript analysis as a tool in inverse metabolic engineering.

Through genome-wide transcript analysis of a reference strain and two recombinant Saccharomyces cerevisiae strains with different rates of galactose uptake, we obtained information about the global transcriptional response to metabolic engineering of the GAL gene regulatory network. One of the recombinant strains overexpressed the gene encoding the transcriptional activator Gal4, and in the other strain the genes encoding Gal80, Gal6, and Mig1, which are negative regulators of the GAL system, were deleted. Even though the galactose uptake rates were significantly different in the three strains, we surprisingly did not find any significant changes in the expression of the genes encoding the enzymes catalyzing the first steps of the pathway (i.e., the genes encoding Gal2, Gal1, Gal7, and Gal10). We did, however, find that PGM2, encoding the major isoenzyme of phosphoglucomutase, was slightly up-regulated in the two recombinant strains with higher galactose uptake rates. This indicated that PGM2 is a target for overexpression in terms of increasing the flux through the Leloir pathway, and through overexpression of PGM2 the galactose uptake rate could be increased by 70% compared to that of the reference strain. Based on our findings, we concluded that phosphoglucomutase plays a key role in controlling the flux through the Leloir pathway, probably due to increased conversion of glucose-1-phosphate to glucose-6-phosphate. This conclusion was supported by measurements of sugar phosphates, which showed that there were increased concentrations of glucose-6-phosphate, galactose-6-phosphate, and fructose-6-phosphate in the strain construct overexpressing PGM2.

Culture Media↗
PubMed1977

Inhibitory action of galactose on phagocytes from normal and hypergalactosemic chicks.

The inhibitory effect of galactose on phagocyte function was investigated in normal and hypergalactosemic chicks by monitoring the in vitro killing of Escherichia coli by leukocytes and the in vivo clearance of colloidal 125I-labeled bovine serum albumin ([125I]BSA) from the circulation. Elevated levels of galactose (30 mM) significantly impaired the bactericidal activities of leukocytes from both control and hypergalactosemic chicks. However, the latter cells were more susceptible to the galactose-dependent inhibition. Leukocytes from hypergalactosemic chicks displayed near-normal bactericidal activity when assayed in vitro under simulated normal conditions in the absence of galactose. Mean corrected phagocytic indexes, obtained from data on the clearance of colloidal [125I]BSA, were calculated to be 0.358 and 0.299 for control and hypergalactosemic chicks, respectively. Moreover, increased concentrations of galactose significantly impaired the bactericidal activity of circulating leukocytes but did not significantly affect the phagocytic activity of the reticuoendothelial system.

Animals↗
PubMed1972

Antibody-mediated modification of the binding properties of a protein related to galactose transport.

A galactose-binding protein related to the mglP transport system of Escherichia coli increases its affinity and binding capacity for the substrate when exposed to both d-galactose and specific antibodies. For this increase to occur, the binding protein has to be in contact with d-galactose for at least 2 min prior to the addition of the antibodies. This reaction was used to show that other substrates of the mglP transport system compete with galactose for a site(s) of the binding protein and that the degree of competition is comparable to that observed in vivo. A model for substrate translocation is presented postulating a cellular component that can induce conformational changes in the galactose-binding protein similar to those caused by antibodies.

Animals↗
PubMed1981

Regulation of galactose operon expression: glucose effects and role of cyclic adenosine 3',5'-monophosphate.

We studied the following two aspects of the glucose effect on galactose operon expression in Escherichia coli K-12: catabolite repression and inducer exclusion. Using both inducible and constitutive strains and measuring the rate of promoter-proximal enzyme synthesis, we found that the galactose operon did not seem to exhibit catabolite repression. The only glucose effect on galactose operon expression which we observed was inducer exclusion, as shown by the existence of diauxic growth in the presence of glucose and galactose. This diauxie was not relieved by cyclic adenosine 3',5'-monophosphate. Cyclic adenosine 3',5'-monophosphate did not seem to be an antagonist of any glucose effect on galactose operon expression; its only effect was to stimulate promoter-distal gene expression.

Cyclic AMP↗